Cosmetic compositions

ABSTRACT

A method for reducing hyaluronidase activity and promoting hyaluronic acid production in skin comprising topically applying to skin in need thereof a composition comprising an effective amount of  Centella asiatica  stem cells to reduce hyaluronidase activity in skin, an effective amount of tetradecyl aminobutyroylvalylamino butyric urea trifluoroacetate to promote hyaluronic acid production in skin, and an effective amount of tripeptide-1 to promote hyaluronic acid production in skin.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/963,886, filed Dec. 9, 2015, which is a continuation of U.S.application Ser. No. 13/468,874, filed May 10, 2012 (issued as U.S. Pat.No. 9,233,062, on Jan. 12, 2016), which claims the benefit of U.S.Provisional Application No. 61/550,813, filed Oct. 24, 2011, U.S.Provisional Application No. 61/495,208, filed Jun. 9, 2011, and U.S.Provisional Application No. 61/484,542, filed May 10, 2011. The contentsof all of the referenced applications are incorporated into thisapplication by reference.

BACKGROUND OF THE INVENTION

A. Field of the Invention

The present invention relates generally to a combination of ingredientsthat can reduce the appearance of deep lines and wrinkles, restorelifted contours, and recapture a youthful volume in the skin. Inparticular, the following combinations were found to work well with oneanother to treat skin in such a manner and to ultimately provide for amore youthful appearance of skin: Combination 1: (1) Centella asiaticastem cells, which can reduce the activity of hyaluronidase in skin; (2)tetradecyl aminobutyroylvalylamino butyric urea trifluoroacetate, whichcan promote the production of hyaluronic acid in skin; and (3)tripeptide-1, which can promote the synthesis of fibronectin and lamininin skin; Combination 2: (1) Centella asiatica stem cells, which canreduce the activity of hyaluronidase in skin; (2) Alpinia galanga leafextract, which can promote the production of hyaluronic acid in skin;and (3) tripeptide-1, which can promote the production of fibronectinand laminin in skin; and Combination 3: (1) Centella asiatica stemcells, which can reduce the activity of hyaluronidase in skin; and (2)tripeptide-1, which can promote the synthesis of fibronectin and lamininin skin.

B. Description of Related Art

Many factors contribute to skin aging such as the actual age of aperson, the amount of exposure to environmental factors (e.g., sunlight, pollution, chemicals, smoke, etc.), and how well a person hastaken care of their skin. In particular, skin aging concerns twoprocesses—intrinsic aging, which is related to the natural aging processand genetic influences, and extrinsic, or accumulated damage due toenvironmental factors such as sun exposure. This combination of factorseventually leads to visible signs of aging, and over time these signsprogress through three stages—early, moderate and advanced.

The early signs of skin aging include the first stages of visible finelines, especially around the eyes, and the beginning of uneven skintone. Cell turnover begins to slow, and this can have a dulling effecton the complexion. Collagen and elastin—while still healthy—can start tosuffer early damage, leaving skin slightly less resilient. If the matrixis left unprotected, wrinkles that are forming underneath the surface ofthe skin will eventually become more noticeable due to damage in thedermal layer. Eyes can occasionally look puffy, and pores appearslightly more noticeable. Typically, this occurs in an age range ofabout 25 to 35 years of age.

The moderate signs of skin aging include more pronounced expressionlines around the eyes, the mouth and on the forehead. Underneath theeyes dark circles can become more noticeable. The skin's supportstructure becomes weaker as less collagen is produced, and elastinfibers begin to lose their ability to “snap” back. Skin loses vitalmoisture more easily, and dark spots can become more of an issue. Finelines on the neck can become more visible, and “marionette” lines oneither side of the mouth can begin to appear. More significant age spotsbegin to surface, eyes may look tired more often, and pores appearlarger. This typically occurs in an age range of about 35 to 50 years ofage.

The advanced signs of skin aging include “static” deep lines andwrinkles that are visible even when the face is at rest. The supportingstructure of collagen and elastin is severely compromised and skinsagging, especially in the cheek and jawline areas, becomes evident. Theneck shows signs of cumulative damage, with the skin becoming loose andmarked by horizontal wrinkles called “tree rings.” Dark spots becomemore prominent, and the eye area can show noticeable crepiness, sagging,puffiness and more pronounced dark circles in addition to a “drooping”upper eyelid. Skin loses its youthful volume and lift due to a loss ofnatural cushioning, and skin dryness is more pronounced as the externalbarrier is compromised, oil production slows and internal moisturelevels drop. Cell turnover slows dramatically, and dead skin cellsremain on the skin's surface which can dull the complexion and makepores more noticeable. The thickness of the skin is also impacted, andas it becomes thinner it's more easily irritated. Typically this occursin an age range of above 50 years of age.

Current products on the market either do not effectively address ageingskin or have skin irritating effects. The inventors, however, havediscovered a unique combination of ingredients that work in a symbioticrelationship with one another to effectively address the signs of early,moderate, and advanced skin ageing.

SUMMARY OF THE INVENTION

The inventors have discovered that particular combinations ofingredients can be used revitalize and rebuild the skin matrix byattacking and up regulating various biochemical pathways. These pathwaysinclude reducing the activity of hyaluronidase in skin, promoting theproduction of hyaluronic acid in skin; and promoting the synthesis offibronectin and laminin in skin.

In one instance, there is disclosed a topical skin compositioncomprising an effective amount of a Centella asiatica stem cells toreduce the activity of hyaluronidase in skin, an effective amount oftetradecyl aminobutyroylvalylamino butyric urea trifluoroacetate orAlpinia galanga leaf extract to promote the production of hyaluronicacid in skin, an effective amount of tripeptide-1 to promote theproduction of fibronectin and laminin in skin, and a dermatologicallyacceptable vehicle. The topical skin composition can include aneffective amount of tetradecyl aminobutyroylvalylamino butyric ureatrifluoroacetate to promote the production of hyaluronic acid in skin.The topical skin composition can include an effective amount of Alpiniagalanga leaf extract to promote the production of hyaluronic acid inskin. The Centella asiatica stem cells can be a mixture of Centellaasiatica stem cells, glycerin, and xanthan gum. The tetradecylaminobutyroylvalylamino butyric urea trifluoroacetate can be a mixtureof tetradecyl aminobutyroylvalylamino butyric urea trifluoroacetate,magnesium chloride, glycerin, and water. The Alpinia galanga leafextract can be a mixture of water, butylene glycol, Alpinia galanga leafextract, xanthan gum, and caprylic/capric triglyceride. The tripeptide-1can be a mixture of tripeptide-1, water, urea, glucose, and guanidineHCL. The composition can include 0.000001 to 10% by weight of Centellaasiatica stem cells, 0.000001 to 10% by weight of tetradecylaminobutyroylvalylamino butyric urea trifluoroacetate or Alpinia galangaleaf extract, and 0.000001 to 10% by weight of tripeptide-1. Inparticular aspects, the amount of said ingredients can be as low as0.000001 and as high as 1%, and more so as low as 0.01 to as high as0.5% by weight. As explained elsewhere, the composition can beformulated in a wide variety of types, non-limiting examples of whichare serums, creams, lotions, cleansers, and the like. In some instances,the compositions can further include any one of, any combination of, orall of Myrciaria jaboticaba extract, Secale cereale seed extract,Spilanthes acmella flower extract, Pisum sativum extract, Alteromonasferment filtrate or extract, and dihyroxymethyl chromone. In otherinstances, the compositions can further include any one of, anycombination of, or all of Secale cereale seed extract, Alteromonasferment filtrate or extract, Myrciaria jaboticaba extract, Arganiaspinosa kernel extract, Asparagopsis armata extract, Ascophyllum nodosumextract, and Rubus fruticosus leaf extract. In yet other instances, thecompositions can further include any one of, any combination of, or allof Magnolia officinalis bark extract or Magnolia grandiflora barkextract, Magnolia biondii bud/flower extract, Brassica campestrissterols, Citrus grandis peel extract, Caprooyl tetrapeptide-3, PisumSativum extract, Hesperidin methyl chalcone, and Palmitoyltetrapeptide-7. In even further instances, the compositions can alsoinclude any one of, any combination of, or all of Silybum marianumextract or silymarin, 4-t-Butylcyclohexanol, Hexylresorcinol, andCestrum latifolium extract. The compositions can further include any oneof, any combination of, or all of retinol, Punica granatum extract orsterols thereof, Codium tomentosum extract, Cinnamomum Cassia barkextract, and Glycyrrhiza glabra (Licorice) root extract. In even otheraspects, the compositions can further include a mixture of maltodextrin,lipase, and subtilisin. In other aspects, the compositions can furtherinclude any one of, any combination of, or all of Secale cereale seedextract, alteromonas ferment filtrate or extract, Codium tomentosumextract, Argania spinosa kernel extract, Asparagopsis armata extract,Ascophyllum nodosum extract, and Rubus fruticosus leaf extract. Thecompositions can further include any one of, any combination of, or allof Magnolia officinalis bark extract or Magnolia grandiflora barkextract, Magnolia biondii bud/flower extract, hesperidin methyl calcone,Pisum sativum extract, Brassica campostris sterols, Citrus grandis peelextract, dipeptide-2, palmitoyl tetrapeptide-7, and ascorbyltetraisopalmitate. The compositions can also include any one of, anycombination of, or all of retinol, Punica granatum extract or sterolsthereof, Codium tomentosum extract, adenosine, Cinnamomum cassia barkextract, adenosine, and Glycyrrhiza glabra root extract. Alsocontemplated is a method for treating skin comprising topically applyingany one of said compositions to skin in need of treatment, whereintopical application of the composition reduces the activity ofhyaluronidase in skin, increases the production of hyaluronic acid inskin, and increases the production of fibronectin and/or laminin inskin. As explained elsewhere, the pathways that the combination ofingredients affect allow it to treat a wide range of skin conditions,non-limiting examples of which include fine line or wrinkle, skin thathas reduced elasticity, loose skin, skin that is deficient in hyaluronicacid production and skin that is deficient in matrix protein production(e.g., fibronectin, laminin, collagen I, collagen III, and/or elastin).In particular instances, the compositions can be applied to theperiorbital area of a person's skin (which is the area adjacent to andaround the eyes). The compositions can be applied to facial skin, neckskin, shoulder skin, arms, legs, hands, and back skin. Also explainedelsewhere, the compositions can be formulated as a leave-on product or arinse of product. In some instances, the compositions remain on the skinfor at least 5, 10, 30, or 60 minutes after topical application, or atleast 12 hours after topical application or at least 24 hours aftertopical application.

In one instance, there is disclosed a topical skin and method for itsuse that includes a dermatologically acceptable vehicle and at leastone, two or all three of the following: an effective amount of aCentella asiatica stem cells to reduce the activity of hyaluronidase inskin; an effective amount of tetradecyl aminobutyroylvalylamino butyricurea trifluoroacetate or Alpinia galanga leaf extract to promote theproduction of hyaluronic acid in skin; and an effective amount oftripeptide-1 to promote the production of fibronectin and laminin inskin.

Another aspect of the present invention includes a combination ofCentella asiatica extract or Centella asiatica meristem cell culture,tetradecyl aminobutyroylvalylamino butyric urea trifluoroacetate, andtripeptide-1, have the ability to increase synthesis of extracellularmatrix proteins (e.g., collagen, elastin, and hyaluronic acid) andproteins localized in the dermal-epidermal junction (e.g., laminin andfibronectin) of the skin. This combination can be placed into acomposition, which can be formulated as a cream, lotion, emulsion,serum, or cleanser, for instance.

In another instance, the inventors have discovered that a combination ofCentella asiatica extract or Centella asiatica meristem cell culture,tetradecyl aminobutyroylvalylamino butyric urea trifluoroacetate,tripeptide-1, Myrciaria jaboticaba extract, Secale cereale seed extract,Spilanthes acmella flower extract, Pisum sativum extract, Alteromonasferment filtrate or extract, and dihyroxymethyl chromone in acomposition can also increase synthesis of extracellular matrix proteins(e.g., collagen, elastin, and hyaluronic acid) and proteins localized inthe dermal-epidermal junction (e.g., laminin and fibronectin) of theskin and provide additional skin benefits. In particular aspects, thiscombination of ingredients has been found to work well with skin locatedon the neck and face. In certain embodiments, a composition having thiscombination of ingredients is formulated as a serum.

In still another embodiment, the inventors have discovered that acombination of Centella asiatica extract or Centella asiatica meristemcell culture, tetradecyl aminobutyroylvalylamino butyric ureatrifluoroacetate, tripeptide-1, Secale cereale seed extract, Alteromonasferment filtrate or extract, Myrciaria jaboticaba extract, Arganiaspinosa kernel extract, Asparagopsis armata extract, Ascophyllum nodosumextract, and Rubus fruticosus leaf extract can also increase synthesisof extracellular matrix proteins (e.g., collagen, elastin, andhyaluronic acid) and proteins localized in the dermal-epidermal junction(e.g., laminin and fibronectin) of the skin and provide additional skinbenefits. In particular aspects, this combination of ingredients hasalso been found to work well with skin located on the neck and face. Incertain embodiments, a composition having this combination ofingredients is formulated as a serum.

In yet another embodiment, the inventors have discovered that acombination of Centella asiatica extract or Centella asiatica meristemcell culture, Magnolia officinalis bark extract or Magnolia grandiflorabark extract, Magnolia biondii bud/flower extract, Brassica campestrissterols, Citrus grandis peel extract, Caprooyl tetrapeptide-3, PisumSativum extract, Hesperidin methyl chalcone, and Palmitoyltetrapeptide-7 can also increase synthesis of extracellular matrixproteins (e.g., collagen, elastin, and hyaluronic acid) and proteinslocalized in the dermal-epidermal junction (e.g., laminin andfibronectin) of the skin and provide additional skin benefits. Inparticular aspects, this combination of ingredients has also been foundto work well with skin located in the periorbital region of the face(e.g., skin around and under the eyes). In certain aspects, thiscombination can reduce the appearance of dark circles under the eye,puffy skin under the eye, sagging or “bags” under the eye, and increaseblood circulation under the eye. In certain embodiments, a compositionhaving this combination of ingredients is formulated as a cream orlotion or emulsion.

In still a further embodiment, the inventors have discovered that acombination of Centella asiatica extract and/or Centella asiaticameristem cell culture, Magnolia officinalis bark extract or Magnoliagrandiflora bark extract, Magnolia biondii bud/flower extract;Hesperidin methyl chalcone, Pisum sativum extract, Citrus grandis peelextract, Dipeptide-2, Palmitoyl tetrapeptide-7, and Caprooyltetrapeptide-3 can also increase synthesis of extracellular matrixproteins (e.g., collagen, elastin, and hyaluronic acid) and proteinslocalized in the dermal-epidermal junction (e.g., laminin andfibronectin) of the skin and provide additional skin benefits. Inparticular aspects, this combination of ingredients has also been foundto work well with skin located in the periorbital region of the face(e.g., skin around and under the eyes). In certain aspects, thiscombination can reduce the appearance of dark circles under the eye,puffy skin under the eye, sagging or “bags” under the eye, and increaseblood circulation under the eye. In certain embodiments, a compositionhaving this combination of ingredients is formulated as a cream orlotion or emulsion.

In yet another embodiment, the inventors have discovered that acombination of tripeptide-1, tetradecyl aminobutyroylvalylamino butyricurea trifluoroacetate, Centella asiatica extract or Centella asiaticameristem cell culture, Silybum marianum extract or silymarin,4-t-Butylcyclohexanol, Hexylresorcinol, and Cestrum latifolium extractcan also increase synthesis of extracellular matrix proteins (e.g.,collagen, elastin, and hyaluronic acid) and proteins localized in thedermal-epidermal junction (e.g., laminin and fibronectin) of the skinand provide additional skin benefits. In certain embodiments, acomposition having this combination of ingredients is formulated as acream or lotion or emulsion. In some instances, the composition canfurther include Ascophyllum nodosum extract and/or Asparagopsis armataextract.

In yet another embodiment, the inventors have discovered that acombination of retinol, Punica granatum extract or sterols thereof,Codium tomentosum extract, Cinnamomum Cassia bark extract, Glycyrrhizaglabra (Licorice) root extract, Centella asiatica extract or Centellaasiatica meristem cell culture, and Tetradecylaminobutyroylvalylaminobutyric urea trifuoroacetate can also increasesynthesis of extracellular matrix proteins (e.g., collagen, elastin, andhyaluronic acid) and proteins localized in the dermal-epidermal junction(e.g., laminin and fibronectin) of the skin and provide additional skinbenefits. In certain embodiments, a composition having this combinationof ingredients is formulated as a cream or lotion or emulsion.

In still another embodiment, the inventors have discovered that acombination of Zymo Clear™ MD (mixture of maltodextrin, lipase, andsubtilisin), tripeptide-1, Tetradecyl aminobutyroylvalylaminobutyricurea trifuoroacetate, and Centella Asiatica extract or Centella asiaticameristem cell culture works particularly well in a skin-cleansing basecomposition. Such a composition can include emulsifiers and/orsurfactants but does not require emulsifiers and/or surfactants.

The inventors have also discovered that a combination of Centellaasiatica extract or Centella asiatica meristem cell culture, Alpiniagalanga leaf extract, and tripeptide-1, have the ability to increasesynthesis of extracellular matrix proteins (e.g., collagen, elastin, andhyaluronic acid) and proteins localized in the dermal-epidermal junction(e.g., laminin and fibronectin) of the skin. This combination can beincluded in a topical skin composition (e.g., cream, lotion, serum, gel,etc.). A person can be identified as having decreased synthesis ofextracellular matrix proteins and/or proteins localized in thedermal-epidermal junction of the skin when compared with skin that hasnormal synthesis of extracellular matrix proteins and/or proteinslocalized in the dermal-epidermal junction of the skin. The compositioncan be used to strengthen the dermal-epidermal junction in sagging,non-elastic, loose, or wrinkled skin.

In another aspect, the inventors have discovered that a combination ofCentella asiatica extract or Centella asiatica meristem cell culture,Alpinia galanga leaf extract, tripeptide-1, Secale cereale seed extract,Alteromonas ferment filtrate or extract, Codium tomentosum extract,Argania spinosa kernel extract, Asparagopsis armata extract, Ascophyllumnodosum extract, and Rubus fruticosus leaf extract can be used toincreases synthesis of extracellular matrix proteins and/or proteinslocalized in the dermal-epidermal junction of the skin. This combinationcan be included in a topical skin composition (e.g., cream, lotion,serum, gel, etc.). A person can be identified as having decreasedsynthesis of extracellular matrix proteins and/or proteins localized inthe dermal-epidermal junction of the skin when compared with skin thathas normal synthesis of extracellular matrix proteins and/or proteinslocalized in the dermal-epidermal junction of the skin. The compositioncan strengthen the dermal-epidermal junction in sagging, non-elastic,loose, or wrinkled skin. This combination works especially well onfacial and neck skin.

Also disclosed is a combination of Magnolia officinalis bark extract orMagnolia grandiflora bark extract, Magnolia biondii bud/flower extract,hesperidin methyl calcone, Pisum sativum extract, Brassica campostrissterols, Citrus grandis peel extract, dipeptide-2, palmitoyltetrapeptide-7, ascorbyl tetraisopalmitate, Centella asiatica extract orCentella asiatica meristem cell culture, and tripeptide-1. In certainaspects, the combination can further include Opuntia tuna fruit extract.This combination can be included in a topical skin composition (e.g.,cream, lotion, serum, gel, etc.). This combination can be used to treatskin in the periorbital region of the face. In particular aspects, thecombination can be applied to wrinkles around the eyes, crow feet, bagsunder the eyes, dark circles under the eye, or skin under the eye. Thecombination can increase blood circulation in the skin when comparedwith untreated skin.

In a further embodiment, there is disclosed a combination of retinol,Punica granatum extract or sterols thereof, Codium tomentosum extract,adenosine, Cinnamomum cassia bark extract, adenosine, Glycyrrhiza glabraroot extract, Centella asiatica extract or Centella asiatica meristemcell culture, tripeptide-1, and Alpinia galanga leaf extract, which canbe used to treat skin. This combination can be included in a topicalskin composition (e.g., cream, lotion, serum, gel, etc.). Thecombination can be used to increase synthesis of extracellular matrixproteins and/or proteins localized in the dermal-epidermal junction ofthe skin. A person can be identified as having decreased synthesis ofextracellular matrix proteins and/or proteins localized in thedermal-epidermal junction of the skin when compared with skin that hasnormal synthesis of extracellular matrix proteins and/or proteinslocalized in the dermal-epidermal junction of the skin. The combinationcan strengthen the dermal-epidermal junction in sagging, non-elastic,loose, or wrinkled skin. In particular aspects, this combination hasbeen found to work best on facial or neck skin.

In still a further aspect, there is disclosed a topical skin compositionthat includes any one of, any combination of, or all of Centellaasiatica extract or Centella asiatica meristem cell culture, tetradecylaminobutyroylvalylamino butyric urea trifluoroacetate, tripeptide-1,and/or Alpinia galanga leaf extract. Also disclosed is a method oftreating a wide variety of skin conditions with compositions have anyone of, any combination of, or all of Centella asiatica extract orCentella asiatica meristem cell culture, tetradecylaminobutyroylvalylamino butyric urea trifluoroacetate, tripeptide-1,and/or Alpinia galanga leaf extract.

The aforementioned combination of ingredients can be used in a widerange of applications to treat or prevent a skin condition. Forinstance, compositions having any of the combinations can be topicallyapplied to skin in need of such treatment (e.g., aged skin, sun damagedskin, dry skin, dirty or oily skin, flaky skin, fine lines or wrinkles,pits or nodules, erythemic skin, sagging skin, skin that produces areduced amount of collagen, elastin, and/or hyaluronic acid, skin thatproduces a reduced amount of laminin and/or fibronectin, skin having adeficient or defective dermal-epidermal junction, etc.), whereintopically application of an effective amount of said combinations cantreat or prevent said skin condition. The effective amount of any one ofthe extracts individually or in combination can be 0.0001 to 20% byweight (or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, or 50%).Additional skin conditions that can be treated or prevented with any oneof the methods and/or compositions of the present can be: chapped skin,pruritus, spider veins, lentigo, age spots, senile purpura, keratosis,melasma, blotches, dermatitis (including, but not limited to seborrheicdermatitis, nummular dermatitis, contact dermatitis, atopic dermatitis,exfoliative dermatitis, perioral dermatitis, and stasis dermatitis),psoriasis, folliculitis, rosacea, acne, impetigo, erysipelas,erythrasma, eczema, sun burns, burned skin, open wounds, and/or skin-inflammatory skin conditions.

In one particular aspect there is disclosed a method of treating orpreventing a fine line or wrinkle comprising topically applying to skinin need thereof any one of the compositions of the present invention,wherein topical application of said composition to a fine line orwrinkle treats said fine line or wrinkle.

In yet another embodiment there is disclosed a method of treating orpreventing erythemic skin or symptoms associated with erythemic skin(e.g., red skin, flushed skin, etc.) comprising topically applying toskin in need thereof any one of the compositions of the presentinvention, wherein topical application of said composition to erythemicskin treats said erythemic skin. Erythema can be caused by skinirritation, an inflammatory response, skin sunburn, electricaltreatments of skin, skin burns, contact allergies, systemic allergies,skin toxicity, exercise, insect stings, bacterial infection, viralinfection, fungal infection, protozoa infection, massage, windburn, andother factors that can cause reddening or flushing of the skin etc. Thecompositions disclosed above and throughout this specification can beused. The compositions can also be used to reducing pain associated witherythema, sensitive skin, or inflamed skin, comprising topicallyapplying to erythemic, sensitive, or inflamed skin a compositioncomprising jaboticaba fruit pulp and/or cashew fruit pulp or extractsthereof.

Also disclosed is a method of tightening or toning skin comprisingtopically applying to skin in need thereof a composition comprising anyone of the compositions of the present invention, wherein topicalapplication of said composition to skin tightens or tones said skin. Thecompositions disclosed above and throughout this specification can beused.

Also disclosed is a method of increasing the integrity of thedermal-epidermal junction (“DEJ”) comprising topically applying any oneof the combination of ingredients or compositions having saidcombinations disclosed throughout this specification to skin. Thismethod can stimulate the production of proteins and enzymes in dermaland epidermal cells that aid in connecting the dermal layer to theepidermal layer. Not wishing to be bound by theory, it is believed thatthe combination of ingredients disclosed throughout the specification(e.g., Centella asiatica extract or Centella asiatica meristem cellculture, tetradecyl aminobutyroylvalylamino butyric ureatrifluoroacetate, and tripeptide-1 or Centella asiatica extract orCentella asiatica meristem cell culture, Alpinia galanga leaf extract,and tripeptide-1) stimulate proteins that are vital to the health of theDEJ (e.g., collagen, elastin. Fibronectin, and laminin).

An additional embodiment includes an injectably acceptable solutioncomprising any one of the aforementioned combination of ingredients. Aninjectably acceptable solution includes a solution that can be safelyinjected into a human or animal.

One embodiment concerns a method of treating or preventing a diseasecomprising administering to a person in need thereof any one of theaforementioned combination of ingredients disclosed throughout thisspecification, wherein the disease is treated or prevented. Non-limitingexamples of diseases include AIDS, an autoimmune disease (e.g.,rheumatoid arthritis, multiple sclerosis, diabetes—insulin-dependent andnon-independent, systemic lupus erythematosus, or Graves disease), acancer (e.g., malignant, benign, metastatic, or precancer), acardiovascular disease (e.g., heart disease, or coronary artery disease,stroke—ischemic and hemorrhagic, or rheumatic heart disease), diseasesof the nervous system, an infection by a pathogenic microorganism (e.g.,Athlete's Foot, Chickenpox, Common cold, Diarrheal diseases, Flu,Genital herpes, Malaria, Meningitis, Pneumonia, Sinusitis, Skindiseases, Strep throat, Tuberculosis, Urinary tract infections, Vaginalinfections, or Viral hepatitis), inflammation (e.g., allergy, orasthma), a prion disease (e.g., CID, kuru, GSS, or FFI), or obesity.

A further embodiment includes a method of treating or preventing hairloss comprising administering to a patient in need thereof a compositioncomprising any one of the afore mentioned combination of ingredientsdisclosed throughout this specification. The composition can be includeda pharmaceutically (whether topical, oral, injectible, etc.) ordermatologically acceptable vehicle, wherein administering to thepatient in need thereof prevents or treats hair loss. Preventing ortreating hair loss can include stimulating hair growth on the scalp, ineyebrows, in eyelashes, or on other regions of the body where hairgrowth is desired. The composition can take the form of an edible pillor gel cap or liquid or powder or foam or spray or aerosolized. Thecomposition can be topically applied, ingested, injected, etc.

The compositions of the present invention can take the form of a pill,gel capsule, spray, foam, topical cream, ointment, gel, or lotion, beaerosolized, or be in powdered form. The compositions can be formulatedas emulsions (e.g., oil-in-water, water-in-oil, silicone-in-water,water-in-silicone, water-in-oil-in-water, oil-in-water,oil-in-water-in-oil, oil-in-water-in-silicone, etc.), creams, lotions,solutions (e.g., aqueous or hydro-alcoholic solutions), anhydrous bases(e.g., lipstick or a powder), gels, ointments, milks, pastes, aerosols,solid forms, eye jellies, etc.. The compositions can also be formulatedfor topical skin application at least 1, 2, 3, 4, 5, 6, 7, or more timesa day during use. In other aspects of the present invention,compositions can be storage stable or color stable, or both. It is alsocontemplated that the viscosity of the composition can be selected toachieve a desired result, e.g., depending on the type of compositiondesired, the viscosity of such composition can be from about 1 cps towell over 1 million cps or any range or integer derivable therein (e.g.,2 cps, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100,200, 300, 400, 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000,6000, 7000, 8000, 9000, 10000, 20000, 30000, 40000, 50000, 60000, 70000,80000, 90000, 100000, 200000, 300000, 400000, 500000, 600000, 700000,800000, 900000, 1000000 cps, etc., as measured on a BrookfieldViscometer using a TC spindle at 2.5 rpm at 25° C.). The compositions ofthe present invention can include any desired amount of jaboticaba orcashew extract or both. The amount of the extracts can individually orcombined be from 0.001, 0.01, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8,0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37,38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55,56, 57, 58, 59, 60, 61, 62, 63, 64, 6, 66, 67, 68, 69, 70, 71, 72, 73,74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91,92, 93, 94, 95, 96, 97, 98, or 99%, or more (or any range or integertherein), by weight or volume of the extract or combination of extracts.The compositions in non-limiting aspects can have a pH of about 6 toabout 9. In other aspects, the pH can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, or 14. The compositions can include a triglyceride.Non-limiting examples include small, medium, and large chaintriglycerides. In certain aspects, the triglyceride is a medium chaintriglyceride (e.g., caprylic capric triglyceride). The compositions canalso include preservatives. Non-limiting examples of preservativesinclude methylparaben, propylparaben, or a mixture of methylparaben andpropylparaben. Compositions of the present invention can have UVA andUVB absorption properties. The compositions can have an sun protectionfactor (SPF) of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25,30, 35, 40, 45, 50, 55, 60, or more, or any integer or derivativetherein. The compositions can be sunscreen lotions, sprays, or creams.

The compositions of the present invention can also include any one of,any combination of, or all of the following additional ingredients:water, a chelating agent, a moisturizing agent, a preservative, athickening agent, a silicone containing compound, an essential oil, astructuring agent, a vitamin, a pharmaceutical ingredient, or anantioxidant, or any combination of such ingredients or mixtures of suchingredients. In certain aspects, the composition can include at leasttwo, three, four, five, six, seven, eight, nine, ten, or all of theseadditional ingredients identified in the previous sentence. Non-limitingexamples of these additional ingredients are identified throughout thisspecification and are incorporated into this section by reference. Theamounts of such ingredients can range from 0.0001% to 99.9% by weight orvolume of the composition, or any integer or range in between asdisclosed in other sections of this specification, which areincorporated into this paragraph by reference.

Also disclosed is a method of lightening skin or evening skin tonecomprising applying the compositions of the present invention to theskin. The method can further comprise identify a person in need oflightening skin or evening skin tone. The methods can further includeinhibiting melanogenesis in a skin cell, inhibiting tyrosinase ortyrosinase synthesis in a skin cell, or inhibiting melanin transport tokeratinocytes in a skin cell. The composition can act as an alphamelanin stimulatory hormone antagonist. The composition can even outpigmentation of the skin. In non-limiting aspect, lightening skin caninclude reducing the appearance of an age spot, a skin discoloration, afreckle, a sun spot, hyper-pigmented skin, etc., by topical applicationof the composition to the age spot, a skin discoloration, a freckle, asun spot, hyper-pigmented skin, etc.

Also disclosed is a method of treating hyperpigmentation comprisingapplying the compositions of the present invention to the skin. Themethod can also comprise identifying a person in need of treatinghyperpigmentation and applying the composition to a portion of the skinexhibiting hyperpigmentation. Additional methods contemplated by theinventors include methods for reducing the appearance of an age spot, askin discoloration, or a freckle, reducing or preventing the appearanceof fine lines or wrinkles in skin, or increasing the firmness of skin byapplying the compositions of the present invention to skin in need ofsuch treatment.

Kits that include the compositions of the present invention are alsocontemplated. In certain embodiments, the composition is comprised in acontainer. The container can be a bottle, dispenser, or package. Thecontainer can dispense a pre-determined amount of the composition. Incertain aspects, the compositions is dispensed in a spray, dollop, orliquid. The container can include indicia on its surface. The indiciacan be a word, an abbreviation, a picture, or a symbol.

Also contemplated is a product comprising a composition of the presentinvention. In non-limiting aspects, the product can be a cosmeticproduct. The cosmetic product can be those described in other sectionsof this specification or those known to a person of skill in the art.Non-limiting examples of products include a moisturizer, a cream, alotion, a skin softener, a foundation, a serum, a cleanser a nightcream, a lipstick, a cleanser, a toner, a sunscreen, a mask, ananti-aging product, a deodorant, an antiperspirant, a perfume, acologne, etc.

It is also contemplated that the compositions disclosed throughout thisspecification can be used as a leave-on or rinse-off composition. By wayof example, a leave-on composition can be one that is topically appliedto skin and remains on the skin for a period of time (e.g., at least 5,6, 7, 8, 9, 10, 20, or 30 minutes, or at least 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours,or over night or throughout the day). Alternatively, a rinse-offcomposition can be a product that is intended to be applied to the skinand then removed or rinsed from the skin (e.g., with water) within aperiod of time such as less than 5, 4, 3, 2, or 1 minute. An example ofa rinse of composition can be a skin cleanser, shampoo, conditioner, orsoap. An example of a leave-on composition can be a skin moisturizer,sunscreen, mask, overnight cream, or a day cream.

It is also contemplated that compositions of the present invention canbe included into food-based products (e.g., beverages, fortified water,energy drinks, nutritional drinks, solid foods, vitamins, supplements,etc.) and pharmaceutical products (e.g., pills, injectible solutions,drugs, etc.). “Supplements” can include vitamins, minerals, herbs orother botanicals, amino acids, enzymes and metabolites. Such supplementsare suitable for oral consumption and can be administered orally.

It is contemplated that any embodiment discussed in this specificationcan be implemented with respect to any method or composition of theinvention, and vice versa. Furthermore, compositions of the inventioncan be used to achieve methods of the invention.

In one embodiment, compositions of the present invention can bepharmaceutically or cosmetically elegant or can have pleasant tactileproperties. “Pharmaceutically elegant,” “cosmetically elegant,” and/or“pleasant tactile properties” describes a composition that hasparticular tactile properties which feel pleasant on the skin (e.g.,compositions that are not too watery or greasy, compositions that have asilky texture, compositions that are non-tacky or sticky, etc.).Pharmaceutically or cosmetically elegant can also relate to thecreaminess or lubricity properties of the composition or to the moistureretaining properties of the composition.

“Acne” includes pimples, black heads, white heads, papules, nodules,pustules, inflammatory lesions, or cysts.

“Topical application” means to apply or spread a composition onto thesurface of lips or keratinous tissue. “Topical skin composition”includes compositions suitable for topical application on lips orkeratinous tissue. Such compositions are typicallydermatologically-acceptable in that they do not have undue toxicity,incompatibility, instability, allergic response, and the like, whenapplied to lips or skin. Topical skin care compositions of the presentinvention can have a selected viscosity to avoid significant dripping orpooling after application to skin.

“Keratinous tissue” includes keratin-containing layers disposed as theoutermost protective covering of mammals and includes, but is notlimited to, lips, skin, hair and nails.

The term “about” or “approximately” are defined as being close to asunderstood by one of ordinary skill in the art, and in one non-limitingembodiment the terms are defined to be within 10%, preferably within 5%,more preferably within 1%, and most preferably within 0.5%.

The term “substantially” and its variations are defined as being largelybut not necessarily wholly what is specified as understood by one ofordinary skill in the art, and in one non-limiting embodimentsubstantially refers to ranges within 10%, within 5%, within 1%, orwithin 0.5%.

The terms “inhibiting” or “reducing” or any variation of these termsincludes any measurable decrease or complete inhibition to achieve adesired result. The terms “promote” or “increase” or any variation ofthese terms includes any measurable increase or production of a proteinor molecule (e.g., matrix proteins such as fibronectin, laminin,collagen, or elastin or molecules such as hyaluronic acid) to achieve adesired result.

The term “effective,” as that term is used in the specification and/orclaims, means adequate to accomplish a desired, expected, or intendedresult.

The use of the word “a” or “an” when used in conjunction with the term“comprising” in the claims and/or the specification may mean “one,” butit is also consistent with the meaning of “one or more,” “at least one,”and “one or more than one.”

As used in this specification and claim(s), the words “comprising” (andany form of comprising, such as “comprise” and “comprises”), “having”(and any form of having, such as “have” and “has”), “including” (and anyform of including, such as “includes” and “include”) or “containing”(and any form of containing, such as “contains” and “contain”) areinclusive or open-ended and do not exclude additional, unrecitedelements or method steps.

The compositions and methods for their use can “comprise,” “consistessentially of,” or “consist of” any of the ingredients or stepsdisclosed throughout the specification. With respect to the transitionalphase “consisting essentially of,” in one non-limiting aspect, a basicand novel characteristic of the compositions and methods disclosed inthis specification includes the compositions' abilities to reduce theactivity of hyaluronidase in skin, promote or increase the production ofhyaluronic acid in skin, and/or promote or increase the production offibronectin and laminin in skin.

Other objects, features and advantages of the present invention willbecome apparent from the following detailed description. It should beunderstood, however, that the detailed description and the examples,while indicating specific embodiments of the invention, are given by wayof illustration only. Additionally, it is contemplated that changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: Before and after picture of skin around the eyes (periorbitalregion) that has been treated with a combination of Centella asiaticastem cells, tetradecyl aminobutyroylvalylamino butyric ureatrifluoroacetate, and tripeptide-1.

FIG. 2: Before and after picture of skin on an individual's foreheadthat has been treated with a combination of Before and after picture ofskin around the eyes (periorbital region) that has been treated with acombination of Centella asiatica stem cells, tetradecylaminobutyroylvalylamino butyric urea trifluoroacetate, and tripeptide-1.Arrows illustrate deep wrinkles in the before picture, which havedisappeared in the after picture. The remaining lines in the before andafter pictures represent fine lines in which said lines have beenreduced in the after picture.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

Skin is in a constant state of degradation and renewal, a process thatis kept in optimal balance with younger-aged skin. With age, however,chronological and environmental factors begin to overwhelm the skin, andthe dermal matrix begins to degrade faster than it can be renewed,thereby upsetting this delicate balance.

The skin matrix is responsible for structural integrity, mechanicalresilience, and stability of the skin. The degradation of the skinmatrix plays an important role in the development of wrinkles and othersigns of skin aging. Some of the more well-known components of the skinmatrix include structural proteins (most notably collagen and elastin),which are vital to skin health and youthfulness. Additional proteins arealso critical to the structure and stability of the skin. Laminin andfibronectin are major proteins in the dermal-epidermal junction (DEJ)(also referred to as the basement membrane). The DEJ is located betweenthe dermis and the epidermis interlocks forming fingerlike projectionscalled rete ridges. The cells of the epidermis receive their nutrientsfrom the blood vessels in the dermis. The rete ridges increase thesurface area of the epidermis that is exposed to these blood vessels andthe needed nutrients. The DEJ provides adhesion of the two tissuecompartments and governs the structural integrity of the skin. Lamininand fibronectin are two structural glycoproteins located in the DEJ.Considered the glue that holds the cells together, laminin andfibronectin are secreted by dermal fibroblasts to help facilitate intra-and inter-cellular adhesion of the epidermal calls to the DEJ.

While collagen and elastin fibers provide tensile strength to the skin,they cannot provide the resilience that the tissue needs over time. Inaddition to the framework of structural proteins, the skin matrix alsoneeds appropriate fillers, which provide mechanical cushioning, holdmoisture, and enhance barrier function. The principal skin matrixfillers are glycans, a class of glucose-based polymers which includehyaluronic acid (also referred to as hyaluronan, hyaluronate, or HA). HAis a major component of the extracellular matrix of skin. The largervolume of water hydration associated with HA is a mechanism formaintaining the normal hydration of skin. Further, reduced amounts of HAcan bring about the appearance of aged skin at a much more acceleratedrate. In this regard, HA has several functions, including binding waterto help retain skin moisture, reducing permeability of extracellularfluid, and supporting mechanical resilience and suppleness of the skin.The content of HA within skin decreases with age (after peaking inadolescence or early adulthood). This contributes to the loss ofmoisture, and the skin becomes thinner and less supple. The loss of HAmay also impair the skin's ability to repair itself and possibly affectsthe synthesis and deposition pattern of other skin matrix components.

In addition to the normal aging process, the amount of HA in skin canalso be effected by hyaluronidase, an enzyme that degrades HA. Reducingthe activity of HA would effectively increase the overall amount of HApresent in skin.

With this backdrop in mind, the inventors discovered a uniquecombination of ingredients that are not only compatible within oneanother, but actually work in a synergistic manner in protecting skinmatrix proteins and HA within the skin. These combinations ofingredients and other aspects of the present invention are described innon-limiting embodiments in the following subsections.

A. Combination #1

In one instance, the inventors have discovered that a combination ofCentella asiatica meristem cell culture, tetradecylaminobutyroylvalylamino butyric urea trifluoroacetate, and tripeptide-1,have the ability to increase synthesis of matrix proteins and contents(e.g., laminin, fibronectin, and hyaluronic acid) of the skin while alsoreducing the activity of hyaluronidase in skin.

Centella asiatica is a small herbaceous annual plant that is native toIndia, Sri Lanka, northern Australia, Indonesia, and parts of Asia.Centella asiatica stem cells are commercially available from Institutodi Ricerche Biotecnologiche (Italy) under the trade name CentellaAsiatic Stems G™. This product includes glycerin, Centella asiaticameristem cell culture, and xanthan gum (INCI name).

Tetradecyl aminobutyroylvalylamino butyric urea trifluoroacetate is apeptide-based ingredient that has the ability to boost hyaluronanproduction and protect existing collagen in the skin. This ingredient iscommercially available from Pentapharm or DSM Nutritional Products AG(Switzerland) under the trade name Syn-Hycan™, which is a mixture ofTetradecyl aminobutyroylvalylamino butyric urea trifluoroacetate,magnesium chloride, and glycerin.

Tripeptide-1 is a synthetic peptide that includes glycine, histidine,and lysine. It has the ability to moisturize skin. This ingredient iscommercially available from a wide range of sources (see InternationalCosmetic Ingredient Dictionary and Handbook, 12^(th) edition, volume 1,pages 458-60 (2008), which is incorporated by reference). In particularinstances, the product, Kollaren® (available from Unipex Innovations(Canada), can be used, which is a mixture of water, urea, glucose,guanidine HCL, and tripeptide-1.

B. Combination #2

In another instance, the inventors have discovered that a combination ofCentella asiatica meristem cell culture, Alpinia galanga leaf extract,and tripeptide-1, also have the ability to increase synthesis of matrixproteins and contents (e.g., laminin, fibronectin, and hyaluronic acid)of the skin while also reducing the activity of hyaluronidase in skin.

Descriptions of Centella asiatica meristem cell culture and tripeptide-1are discussed above and incorporated by reference. As for Alpiniagalanga leaf extract, the plant Alpinia galanga is in the ginger familyand is native to South Asia and Indonesia. The leaf portion of thisplant can be used in the context of the present invention (at theexclusion of other portions of the plant). The extract can be an aqueousextract, a glycolic extract, an alcoholic extract, or any combinationthereof. Further the extract is commercially available from BASF (USA)under the trade name HYALUFIX™ GL, which is a mixture of water, butyleneglycol, Alpinia galanga leaf extract, xanthan gum, and caprylic/caprictriglyceride.

C. Combination #3

In a further instance, the inventors have discovered that a combinationof Centella asiatica meristem cell culture with tripeptide-1 has theability to increase synthesis of matrix proteins and contents (e.g.,laminin, fibronectin, and hyaluronic acid) of the skin while alsoreducing the activity of hyaluronidase in skin. These ingredients aredescribed above and incorporated into this section by reference.

D. Additional Combinations

The inventors further discovered additional combinations of ingredientscan be added to the above-mentioned ingredients to create multi-purposescosmetic products. The following additional combinations have been foundto be compatible and to work well in cosmetic compositions ranging fromeye creams, day creams, night creams, serums, and cleansers.

For instance, a combination that can be used with any one ofcombinations 1-3 is that of Myrciaria jaboticaba extract, Secale cerealeseed extract, Spilanthes acmella flower extract, Pisum sativum extract,Alteromonas ferment filtrate or extract, and dihyroxymethyl chromone,which can provide additional skin benefits. In particular aspects, thiscombination of ingredients has been found to work well with skin locatedon the neck and face. In certain embodiments, a composition having thiscombination of ingredients is formulated as a serum. Myrciariajaboticaba extract is obtained from the Brazilian Grape Tree, which is afruit-bearing tree native to Argentina, Brazil and Paraguay. The fruitportion (i.e., Myrciaria jaboticaba fruit extract) is particularlyuseful in the context of the present invention. The fruit has a purplishblack skin, with a white pulp. It can be eaten raw or be used to makejellies and plain juice or wine. The inventors discovered that the pulpportion of Jaboticaba has the ability to inhibit both COX-1 and TNF-α inskin cells, while also increasing the synthesis of hyaluronic acid insuch cells. Jaboticaba fruit and fruit extract are commerciallyavailable from LabCat, the International division of LaboratorioCatarinense (Brazil). Further, a person of ordinary skill in the artwould be able to obtain jaboticaba and cashew fruit pulp by mechanicalseparating the pulp from the other parts of the plants, respectively. Asfor Secale cereale seed extract, it is commercially available from awide range of sources (see International Cosmetic Ingredient Dictionaryand Handbook, 12^(th) edition, volume 2, pages 2452-53 (2008), which isincorporated by reference). In particular instances, the product soldunder the trade name Coheliss from Silab (France) is particularly usefulwith the combinations of the present invention. Secale cereal is a grassthat is grown worldwide. The seeds of this grass can be used to obtainthe extract. With respect to Spilanthes acmella flower extract, it toois commercially available from a wide range of sources (seeInternational Cosmetic Ingredient Dictionary and Handbook, 12^(th)edition, volume 2, pages 2633-34 (2008), which is incorporated byreference). Spilanthes acmella is a flowering herb that is native totropical regions of Brazil. Turning to Pisum sativum extract, it iscommercially available from a wide range of sources (see InternationalCosmetic Ingredient Dictionary and Handbook, 12^(th) edition, volume 2,page 2042 (2008), which is incorporated by reference). Alteromonasferment filtrate or extract is commercially available from a wide rangeof sources (see International Cosmetic Ingredient Dictionary andHandbook, 12^(th) edition, volume 1, page 116 (2008), which isincorporated by reference). This ingredient is obtained by fermentingAlteromonas macleodii, a deep-sea, mesohphilic, heterotrophic bacterium.In particular aspects, the commercially product Abyssine® sold by AtriumInnovations (France) can be used. Dihyroxymethyl chromone is a chemicalcompound that can be used as an anti-wrinkle ingredient. The chemicalstructure of this compound is:

This compound is commercially available from a wide range of sources(e.g., RonaCare® Luremin™, which is sold by EMD Chemicals Inc. (USA)).

Another combination that can be used with any one of combinations 1-3 isSecale cereale seed extract, Alteromonas ferment filtrate or extract,Myrciaria jaboticaba extract, Argania spinosa kernel extract,Asparagopsis armata extract, Ascophyllum nodosum extract, and Rubusfruticosus leaf extract. In particular aspects, this combination ofingredients has also been found to work well with skin located on theneck and face. In certain embodiments, a composition having thiscombination of ingredients is formulated as a serum. Argania spinosakernel extract can be obtained from the kernel of the Argan tree, whichis native to the Mediterranean region. This extract is commerciallyavailable from a wide range of sources (see International CosmeticIngredient Dictionary and Handbook, 12^(th) edition, volume 1, page 198(2008), which is incorporated by reference). In particular aspects, theproduct Argatensyl LS™ from Laboratoires Serobiologiques (France) can beused with the combinations of the present invention. Asparagopsis armataextract is obtained from red alga and is commercially available from awide range of sources (see International Cosmetic Ingredient Dictionaryand Handbook, 12^(th) edition, volume 1, page 214 (2008), which isincorporated by reference). In particular aspects, the product Aldavine™sold by Unipex Innovations (Canada) can be used with the combinations ofthe present invention. Aldavine is a combination of water, Ascophyllumnodosum extract, Asparagopsis armata extract, and sorbitol. With respectto Rubus fruticous leaf extract, it can be obtained by extraction of theleaf of Rubus fruiticous, which is a blackberry plant native to theNorthern hemisphere and South America. It is commercially available froma wide range of sources (see International Cosmetic IngredientDictionary and Handbook, 12^(th) edition, volume 2, page 2399 (2008),which is incorporated by reference).

Another combination that can be used with any one of combinations 1-3 isthat of Magnolia officinalis bark extract or Magnolia grandiflora barkextract, Magnolia biondii bud/flower extract, Brassica campestrissterols, Citrus grandis peel extract, Caprooyl tetrapeptide-3, PisumSativum extract, Hesperidin methyl chalcone, and Palmitoyltetrapeptide-7. In particular aspects, this combination of ingredientshas also been found to work well with skin located in the periorbitalregion of the face (e.g., skin around and under the eyes). In certainaspects, this combination can reduce the appearance of dark circlesunder the eye, puffy skin under the eye, sagging or “bags” under theeye, and increase blood circulation under the eye. In certainembodiments, a composition having this combination of ingredients isformulated as a cream or lotion or emulsion.

A further combination that can be used with any one of combinations 1-3is that of Magnolia officinalis bark extract or Magnolia grandiflorabark extract, Magnolia biondii bud/flower extract, Hesperidin methylchalcone, Pisum sativum extract, Citrus grandis peel extract,Dipeptide-2, Palmitoyl tetrapeptide-7, and Caprooyl tetrapeptide-3. Inparticular aspects, this combination of ingredients has also been foundto work well with skin located in the periorbital region of the face(e.g., skin around and under the eyes). In certain aspects, thiscombination can reduce the appearance of dark circles under the eye,puffy skin under the eye, sagging or “bags” under the eye, and increaseblood circulation under the eye. In certain embodiments, a compositionhaving this combination of ingredients is formulated as a cream orlotion or emulsion.

Magnolia officinalis bark extract or Magnolia grandiflora bark extractcan be obtained from the bark of the magnolia tree for the respectivespecies. Similarly, Magnolia biondii bud/flower extract is also obtainedfrom the magnolia tree. These extracts are commercially available from awide range of sources (see International Cosmetic Ingredient Dictionaryand Handbook, 12^(th) edition, volume 2, pages 1499-50 (2008), which isincorporated by reference). With respect to Brassica campestris sterols,this ingredient is commercially available from a wide range of sources(see International Cosmetic Ingredient Dictionary and Handbook, 12^(th)edition, volume 1, page 314 (2008), which is incorporated by reference).This ingredient is a mixture of sterols obtained from Brassicacampestris (Rapeseed) oil. Turning to Citrus grandis peel extract, it isalso commercially available from a wide range of sources (seeInternational Cosmetic Ingredient Dictionary and Handbook, 12^(th)edition, volume 1, page 610 (2008), which is incorporated by reference).This extract is obtained from the peel of Citrus grandis. Caprooyltetrapeptide-3 is the reaction product of tetrapeptide -3 (peptidehaving glycine, histidine, and lysine) and caproic acid. It iscommercially available from Unipex Innovations (Canada) under the tradename ChroNOline™, which is a combination of glycerin, water, dextran,and caprooyl tetrapeptide-3. Hesperidin methyl chalcone is a chemicalcompound that is commercially available from a wide range of sources(see International Cosmetic Ingredient Dictionary and Handbook, 12^(th)edition, volume 1, page 1146 (2008), which is incorporated byreference). In one aspect, this ingredient can be obtained from usingSederama SAS's (France) mixture sold under the trade name Eyeliss™,which is a combination of water, glycerin, hesperidin methyl chalcone,steareth-20, dipeptide-2 (valyl-tryptophane), and palmitoyltetrapeptide-7 (Pal-GQPR). Palmitoyl tetrapeptide-7, which is thereaction product of palmitic acid and a synthetic peptide containingglycine, glutamine, proline, and arginine), is commercially availablefrom a wide range of sources (see International Cosmetic IngredientDictionary and Handbook, 12^(th) edition, volume 2, page 1767 (2008),which is incorporated by reference). In one aspect, this ingredient canbe obtained from using Sederama SAS's (France) mixture sold under thetrade name Eyeliss™, which is a combination of water, glycerin,hesperidin methyl chalcone, steareth-20, dipeptide-2(valyl-tryptophane), and palmitoyl tetrapeptide-7 (Pal-GQPR).Dipeptide-2, is a synthetic peptide containing valine and tryptophan. Itis commercially available from a wide range of sources (seeInternational Cosmetic Ingredient Dictionary and Handbook, 12^(th)edition, volume 1, page 855 (2008), which is incorporated by reference).

A further combination that can be used with any one of combinations 1-3is Silybum marianum extract or silymarin, 4-t-Butylcyclohexanol,Hexylresorcinol, and Cestrum latifolium extract. In certain embodiments,a composition having this combination of ingredients is formulated as acream or lotion or emulsion. In some instances, the composition canfurther include Ascophyllum nodosum extract and/or Asparagopsis armataextract. Silybum marianum extract or silymarin, it is commerciallyavailable from a wide range of sources (see International CosmeticIngredient Dictionary and Handbook, 12^(th) edition, volume 2, page 2478(2008), which is incorporated by reference). It is obtained from theextraction of lady's thistly, Silybum marianum. An active ingredient inthe extract is silymarin. In particular aspects, Pronalen Silymarin HSC™from Provital S.A. (Spain) can be used. With respect to4-t-Butylcyclohexanol, it is a compound having the following chemicalstructure:

It is commercially available from a wide range of sources (seeInternational Cosmetic Ingredient Dictionary and Handbook, 12^(th)edition, volume 1, page 331 (2008), which is incorporated by reference).Hexylresorcinol is a compound having the following chemical structure:

It is commercially available from a wide range of sources (seeInternational Cosmetic Ingredient Dictionary and Handbook, 12^(th)edition, volume 1, page 1158 (2008), which is incorporated byreference). As for Cestrum latifolium extract, it is obtained from theCestrum latifolium plant, which is native to the tropical regions of theAmericas. It is commercially available from BASF Corporation (USA) underthe trade name Symbiocell™.

Yet another combination that can be used with any one of combinations1-3 is that of retinol, Punica granatum extract or sterols thereof,Codium tomentosum extract, Cinnamomum Cassia bark extract, andGlycyrrhiza glabra (Licorice) root extract. In certain embodiments, acomposition having this combination of ingredients is formulated as acream or lotion or emulsion. Retinol, a form of vitamin A, has thefollowing chemical structure:

Retinol is commercially available from a wide range of sources (seeInternational Cosmetic Ingredient Dictionary and Handbook, 12^(th)edition, volume 2, page 2363 (2008), which is incorporated byreference). In particular instances, the retinol can be encapsulated bymeans known in the art or described in this specification. With respectto Punica granatum extract or sterols thereof, this ingredient iscommercially available from a wide range of sources (see InternationalCosmetic Ingredient Dictionary and Handbook, 12^(th) edition, volume 2,pages 2315-17 (2008), which is incorporated by reference). In particularinstances, Punica granatum sterols sold under the trade name ABSPomegranate Sterols by Active Concepts (USA) can be used. Codiumtomentosum extract, which is extract from algae, is commerciallyavailable from a wide range of sources (see International CosmeticIngredient Dictionary and Handbook, 12^(th) edition, volume 1, page 650(2008), which is incorporated by reference). In particular embodiments,Codiavelane™ from BiotechMarine can be used. Cinnamomum Cassia barkextract is obtained via extraction of the bark from Cinnamomum cassia.It is commercially available from a wide range of sources (seeInternational Cosmetic Ingredient Dictionary and Handbook, 12^(th)edition, volume 1, page 584 (2008), which is incorporated by reference).Glycyrrhiza glabra (Licorice) root extract is obtained via extraction ofthe root from Glycyrrhiza glabra. It is commercially available from awide range of sources (see International Cosmetic Ingredient Dictionaryand Handbook, 12^(th) edition, volume 1, pages 1100-01 (2008), which isincorporated by reference).

Another ingredient that can be used with any one of combinations 1-3above is Zymo Clear™ MD (mixture of maltodextrin, lipase, andsubtilisin). Such a combination has been found to work particularly wellin a skin-cleansing base composition. Such a composition can includeemulsifiers and/or surfactants but does not require emulsifiers and/orsurfactants. Zymo Clear™ MD it is a mixture of maltodextrin, lipase, andsubtilisin that is commercially available from Rahn AG (Switzerland).

Another combination that can be used with any one of combinations 1-3 isSecale cereale seed extract, Alteromonas ferment filtrate or extract,Codium tomentosum extract, Argania spinosa kernel extract, Asparagopsisarmata extract, Ascophyllum nodosum extract, and Rubus fruticosus leafextract. In particular aspects, this combination of ingredients has beenfound to work well with skin located on the neck and face. In certainembodiments, a composition having this combination of ingredients isformulated as a serum.

A further combination that can be used with any one of combinations 1-3is Magnolia officinalis bark extract or Magnolia grandiflora barkextract, Magnolia biondii bud/flower extract, hesperidin methyl calcone,Pisum sativum extract, Brassica campostris sterols, Citrus grandis peelextract, dipeptide-2, palmitoyl tetrapeptide-7, and ascorbyltetraisopalmitate. In further aspects, the combination can furtherinclude Opuntia tuna fruit extract. In particular aspects, thiscombination of ingredients has also been found to work well with skinlocated in the periorbital region of the face (e.g., skin around andunder the eyes). In certain aspects, this combination can reduce theappearance of dark circles under the eye, puffy skin under the eye,sagging or “bags” under the eye, and increase blood circulation underthe eye. In certain embodiments, a composition having this combinationof ingredients is formulated as a cream or lotion or emulsion. Ascorbyltetraisopalmitate is the tetraester of ascorbic acid and isopalmiticacid. It is commercially available from a wide range of sources (seeInternational Cosmetic Ingredient Dictionary and Handbook, 12^(th)edition, volume 1, pages 212-213 (2008), which is incorporated byreference). As for Opuntia tuna fruit extract, it is the extract fromthe fruit of Opuntia tuna. It is commercially available from a widerange of sources (see International Cosmetic Ingredient Dictionary andHandbook, 12^(th) edition, volume 2, page 1731 (2008), which isincorporated by reference).

In still another combination that can be used with any one ofcombinations 1-3 is retinol, Punica granatum extract or sterols thereof,Codium tomentosum extract, Cinnamomum Cassia bark extract, adenosine,and Glycyrrhiza glabra (Licorice) root extract. In certain embodiments,a composition having this combination of ingredients is formulated as acream or lotion or emulsion. Adenosine is a heterocyclic organiccompound generally conforming to the following structure:

Adenosine is commercially available from a wide range of sources (seeInternational Cosmetic Ingredient Dictionary and Handbook, 12^(th)edition, volume 1, page 60 (2008), which is incorporated by reference).

E. Compositions of the Present Invention

It is contemplated that the compositions of the present invention caninclude any amount of the ingredients. The compositions can also includeany number of combinations of additional ingredients describedthroughout this specification (e.g., pigments, or additional cosmetic orpharmaceutical ingredients). The concentrations of the any ingredientwithin the compositions can vary. In non-limiting embodiments, forexample, the compositions can comprise, consisting essentially of, orconsist of, in their final form, for example, at least about 0.0001%,0.0002%, 0.0003%, 0.0004%, 0.0005%, 0.0006%, 0.0007%, 0.0008%, 0.0009%,0.0010%, 0.0011%, 0.0012%, 0.0013%, 0.0014%, 0.0015%, 0.0016%, 0.0017%,0.0018%, 0.0019%, 0.0020%, 0.0021%, 0.0022%, 0.0023%, 0.0024%, 0.0025%,0.0026%, 0.0027%, 0.0028%, 0.0029%, 0.0030%, 0.0031%, 0.0032%, 0.0033%,0.0034%, 0.0035%, 0.0036%, 0.0037%, 0.0038%, 0.0039%, 0.0040%, 0.0041%,0.0042%, 0.0043%, 0.0044%, 0.0045%, 0.0046%, 0.0047%, 0.0048%, 0.0049%,0.0050%, 0.0051%, 0.0052%, 0.0053%, 0.0054%, 0.0055%, 0.0056%, 0.0057%,0.0058%, 0.0059%, 0.0060%, 0.0061%, 0.0062%, 0.0063%, 0.0064%, 0.0065%,0.0066%, 0.0067%, 0.0068%, 0.0069%, 0.0070%, 0.0071%, 0.0072%, 0.0073%,0.0074%, 0.0075%, 0.0076%, 0.0077%, 0.0078%, 0.0079%, 0.0080%, 0.0081%,0.0082%, 0.0083%, 0.0084%, 0.0085%, 0.0086%, 0.0087%, 0.0088%, 0.0089%,0.0090%, 0.0091%, 0.0092%, 0.0093%, 0.0094%, 0.0095%, 0.0096%, 0.0097%,0.0098%, 0.0099%, 0.0100%, 0.0200%, 0.0250%, 0.0275%, 0.0300%, 0.0325%,0.0350%, 0.0375%, 0.0400%, 0.0425%, 0.0450%, 0.0475%, 0.0500%, 0.0525%,0.0550%, 0.0575%, 0.0600%, 0.0625%, 0.0650%, 0.0675%, 0.0700%, 0.0725%,0.0750%, 0.0775%, 0.0800%, 0.0825%, 0.0850%, 0.0875%, 0.0900%, 0.0925%,0.0950%, 0.0975%, 0.1000%, 0.1250%, 0.1500%, 0.1750%, 0.2000%, 0.2250%,0.2500%, 0.2750%, 0.3000%, 0.3250%, 0.3500%, 0.3750%, 0.4000%, 0.4250%,0.4500%, 0.4750%, 0.5000%, 0.5250%, 0.0550%, 0.5750%, 0.6000%, 0.6250%,0.6500%, 0.6750%, 0.7000%, 0.7250%, 0.7500%, 0.7750%, 0.8000%, 0.8250%,0.8500%, 0.8750%, 0.9000%, 0.9250%, 0.9500%, 0.9750%, 1.0%, 1.1%, 1.2%,1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%,2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%,3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%,4.9%, 5.0%, 5.1%, 5.2%, 5.3%, 5.4%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9%, 6.0%,6.1%, 6.2%, 6.3%, 6.4%, 6.5%, 6.6%, 6.7%, 6.8%, 6.9%, 7.0%, 7.1%, 7.2%,7.3%, 7.4%, 7.5%, 7.6%, 7.7%, 7.8%, 7.9%, 8.0%, 8.1%, 8.2%, 8.3%, 8.4%,8.5%, 8.6%, 8.7%, 8.8%, 8.9%, 9.0%, 9.1%, 9.2%, 9.3%, 9.4%, 9.5%, 9.6%,9.7%, 9.8%, 9.9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%,21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 35%, 40%, 45%, 50%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% or any range derivabletherein, of at least one of the ingredients that are mentionedthroughout the specification and claims. In non-limiting aspects, thepercentage can be calculated by weight or volume of the totalcomposition. A person of ordinary skill in the art would understand thatthe concentrations can vary depending on the addition, substitution,and/or subtraction of ingredients in a given composition.

F. Vehicles

The compositions of the present invention can be incorporated into alltypes of vehicles. Non-limiting examples include emulsions (e.g.,water-in-oil, water-in-oil-in-water, oil-in-water, silicone-in-water,water-in-silicone, oil-in-water-in-oil, oil-in-water-in-siliconeemulsions), creams, lotions, solutions (both aqueous andhydro-alcoholic), anhydrous bases (such as lipsticks and powders), gels,and ointments. Variations and other appropriate vehicles will beapparent to the skilled artisan and are appropriate for use in thepresent invention. In certain aspects, it is important that theconcentrations and combinations of the compounds, ingredients, andagents be selected in such a way that the combinations are chemicallycompatible and do not form complexes which precipitate from the finishedproduct.

G. Cosmetic Products and Articles of Manufacture

The composition of the present invention can also be used in manycosmetic products including, but not limited to, lip sticks, lip balms,lip glosses, sunscreen products, sunless skin tanning products, hairproducts, finger nail products, moisturizing creams, skin benefit creamsand lotions, softeners, day lotions, gels, ointments, foundations, nightcreams, cleansers, toners, masks, or other known cosmetic products orapplications. Additionally, the cosmetic products can be formulated asleave-on or rinse-off products. In certain aspects, the compositions ofthe present invention are stand-alone products.

H. Additional Ingredients

In addition to the combination of ingredients disclosed by theinventors, the compositions can also include additional ingredients suchas cosmetic ingredients and pharmaceutical active ingredients.Non-limiting examples of these additional ingredients are described inthe following subsections.

1. Cosmetic Ingredients

The CTFA International Cosmetic Ingredient Dictionary and Handbook (2004and 2008) describes a wide variety of non-limiting cosmetic ingredientsthat can be used in the context of the present invention. Examples ofthese ingredient classes include: fragrances (artificial and natural),dyes and color ingredients (e.g., Blue 1, Blue 1 Lake, Red 40, titaniumdioxide, D&C blue no. 4, D&C green no. 5, D&C orange no. 4, D&C red no.17, D&C red no. 33, D&C violet no. 2, D&C yellow no. 10, and D&C yellowno. 11), adsorbents, lubricants, solvents, moisturizers (including,e.g., emollients, humectants, film formers, occlusive agents, and agentsthat affect the natural moisturization mechanisms of the skin),water-repellants, UV absorbers (physical and chemical absorbers such asparaaminobenzoic acid (“PABA”) and corresponding PABA derivatives,titanium dioxide, zinc oxide, etc.), essential oils, vitamins (e.g. A,B, C, D, E, and K), trace metals (e.g. zinc, calcium and selenium),anti-irritants (e.g. steroids and non-steroidal anti-inflammatories),botanical extracts (e.g. aloe vera, chamomile, cucumber extract, ginkgobiloba, ginseng, and rosemary), anti-microbial agents, antioxidants(e.g., BHT and tocopherol), chelating agents (e.g., disodium EDTA andtetrasodium EDTA), preservatives (e.g., methylparaben andpropylparaben), pH adjusters (e.g., sodium hydroxide and citric acid),absorbents (e.g., aluminum starch octenylsuccinate, kaolin, corn starch,oat starch, cyclodextrin, talc, and zeolite), skin bleaching andlightening agents (e.g., hydroquinone and niacinamide lactate),humectants (e.g., sorbitol, urea, and manitol), exfoliants,waterproofing agents (e.g., magnesium/aluminum hydroxide stearate), skinconditioning agents (e.g., aloe extracts, allantoin, bisabolol,ceramides, dimethicone, hyaluronic acid, and dipotassium glycyrrhizate).Non-limiting examples of some of these ingredients are provided in thefollowing subsections.

a. UV Absorption Agents

UV absorption agents that can be used in combination with thecompositions of the present invention include chemical and physicalsunblocks. Non-limiting examples of chemical sunblocks that can be usedinclude para-aminobenzoic acid (PABA), PABA esters (glyceryl PABA,amyldimethyl PABA and octyldimethyl PABA), butyl PABA, ethyl PABA, ethyldihydroxypropyl PABA, benzophenones (oxybenzone, sulisobenzone,benzophenone, and benzophenone-1 through 12), cinnamates (octylmethoxycinnamate, isoamyl p-methoxycinnamate, octylmethoxy cinnamate,cinoxate, diisopropyl methyl cinnamate, DEA-methoxycinnamate, ethyldiisopropylcinnamate, glyceryl octanoate dimethoxycinnamate and ethylmethoxycinnamate), cinnamate esters, salicylates (homomethyl salicylate,benzyl salicylate, glycol salicylate, isopropylbenzyl salicylate, etc.),anthranilates, ethyl urocanate, homosalate, octisalate, dibenzoylmethanederivatives (e.g., avobenzone), octocrylene, octyl triazone, digalloytrioleate, glyceryl aminobenzoate, lawsone with dihydroxyacetone,ethylhexyl triazone, dioctyl butamido triazone, benzylidene malonatepolysiloxane, terephthalylidene dicamphor sulfonic acid, disodium phenyldibenzimidazole tetrasulfonate, diethylamino hydroxybenzoyl hexylbenzoate, bis diethylamino hydroxybenzoyl benzoate, bisbenzoxazoylphenyl ethylhexylimino triazine, drometrizole trisiloxane,methylene bis-benzotriazolyl tetramethylbutyiphenol, andbis-ethylhexyloxyphenol methoxyphenyltriazine,4-methylbenzylidenecamphor, and isopentyl 4-methoxycinnamate.Non-limiting examples of physical sunblocks include, kaolin, talc,petrolatum and metal oxides (e.g., titanium dioxide and zinc oxide).

b. Moisturizing Agents

Non-limiting examples of moisturizing agents that can be used with thecompositions of the present invention include amino acids, chondroitinsulfate, diglycerin, erythritol, fructose, glucose, glycerin, glycerolpolymers, glycol, 1,2,6-hexanetriol, honey, hyaluronic acid,hydrogenated honey, hydrogenated starch hydrolysate, inositol, lactitol,maltitol, maltose, mannitol, natural moisturizing factor, PEG-15butanediol, polyglyceryl sorbitol, salts of pyrollidone carboxylic acid,potassium PCA, propylene glycol, sodium glucuronate, sodium PCA,sorbitol, sucrose, trehalose, urea, and xylitol.

Other examples include acetylated lanolin, acetylated lanolin alcohol,alanine, algae extract, aloe barbadensis, aloe-barbadensis extract, aloebarbadensis gel, althea officinalis extract, apricot (prunus armeniaca)kernel oil, arginine, arginine aspartate, arnica montana extract,aspartic acid, avocado (persea gratissima) oil, barrier sphingolipids,butyl alcohol, beeswax, behenyl alcohol, beta-sitosterol, birch (betulaalba) bark extract, borage (borago officinalis) extract, butcherbroom(ruscus aculeatus) extract, butylene glycol, calendula officinalisextract, calendula officinalis oil, candelilla (euphorbia cerifera) wax,canola oil, caprylic/capric triglyceride, cardamon (elettariacardamomum) oil, carnauba (copernicia cerifera) wax, carrot (daucuscarota sativa) oil, castor (ricinus communis) oil, ceramides, ceresin,ceteareth-5, ceteareth-12, ceteareth-20, cetearyl octanoate, ceteth-20,ceteth-24, cetyl acetate, cetyl octanoate, cetyl palmitate, chamomile(anthemis nobilis) oil, cholesterol, cholesterol esters, cholesterylhydroxystearate, citric acid, clary (salvia sclarea) oil, cocoa(theobroma cacao) butter, coco-caprylate/caprate, coconut (cocosnucifera) oil, collagen, collagen amino acids, corn (zea mays)oil, fattyacids, decyl oleate, dimethicone copolyol, dimethiconol, dioctyladipate, dioctyl succinate, dipentaerythrityl hexacaprylate/hexacaprate,DNA, erythritol, ethoxydiglycol, ethyl linoleate, eucalyptus globulusoil, evening primrose (oenothera biennis) oil, fatty acids, geraniummaculatum oil, glucosamine, glucose glutamate, glutamic acid,glycereth-26, glycerin, glycerol, glyceryl distearate, glycerylhydroxystearate, glyceryl laurate, glyceryl linoleate, glycerylmyristate, glyceryl oleate, glyceryl stearate, glyceryl stearate SE,glycine, glycol stearate, glycol stearate SE, glycosaminoglycans, grape(vitis vinifera) seed oil, hazel (corylus americana) nut oil, hazel(corylus avellana) nut oil, hexylene glycol, hyaluronic acid, hybridsafflower (carthamus tinctorius) oil, hydrogenated castor oil,hydrogenated coco-glycerides, hydrogenated coconut oil, hydrogenatedlanolin, hydrogenated lecithin, hydrogenated palm glyceride,hydrogenated palm kernel oil, hydrogenated soybean oil, hydrogenatedtallow glyceride, hydrogenated vegetable oil, hydrolyzed collagen,hydrolyzed elastin, hydrolyzed glycosaminoglycans, hydrolyzed keratin,hydrolyzed soy protein, hydroxylated lanolin, hydroxyproline, isocetylstearate, isocetyl stearoyl stearate, isodecyl oleate, isopropylisostearate, isopropyl lanolate, isopropyl myristate, isopropylpalmitate, isopropyl stearate, isostearamide DEA, isostearic acid,isostearyl lactate, isostearyl neopentanoate, jasmine (jasminumofficinale) oil, jojoba (buxus chinensis) oil, kelp, kukui (aleuritesmoluccana) nut oil, lactamide MEA, laneth-16, laneth-10 acetate,lanolin, lanolin acid, lanolin alcohol, lanolin oil, lanolin wax,lavender (lavandula angustifolia) oil, lecithin, lemon (citrus medicalimonum) oil, linoleic acid, linolenic acid, macadamia ternifolia nutoil, maltitol, matricaria (chamomilla recutita) oil, methyl glucosesesquistearate, methylsilanol PCA, mineral oil, mink oil, mortierellaoil, myristyl lactate, myristyl myristate, myristyl propionate,neopentyl glycol dicaprylate/dicaprate, octyldodecanol, octyldodecylmyristate, octyldodecyl stearoyl stearate, octyl hydroxystearate, octylpalmitate, octyl salicylate, octyl stearate, oleic acid, olive (oleaeuropaea) oil, orange (citrus aurantium dulcis) oil, palm (elaeisguineensis) oil, palmitic acid, pantethine, panthenol, panthenyl ethylether, paraffin, PCA, peach (prunus persica) kernel oil, peanut (arachishypogaea) oil, PEG-8 C12-18 ester, PEG-15 cocamine, PEG-150 distearate,PEG-60 glyceryl isostearate, PEG-5 glyceryl stearate, PEG-30 glycerylstearate, PEG-7 hydrogenated castor oil, PEG-40 hydrogenated castor oil,PEG-60 hydrogenated castor oil, PEG-20 methyl glucose sesquistearate,PEG40 sorbitan peroleate, PEG-5 soy sterol, PEG-10 soy sterol, PEG-2stearate, PEG-8 stearate, PEG-20 stearate, PEG-32 stearate, PEG40stearate, PEG-50 stearate, PEG-100 stearate, PEG-150 stearate,pentadecalactone, peppermint (mentha piperita) oil, petrolatum,phospholipids, polyamino sugar condensate, polyglyceryl-3 diisostearate,polyquaternium-24, polysorbate 20, polysorbate 40, polysorbate 60,polysorbate 80, polysorbate 85, potassium myristate, potassiumpalmitate, propylene glycol, propylene glycol dicaprylate/dicaprate,propylene glycol dioctanoate, propylene glycol dipelargonate, propyleneglycol laurate, propylene glycol stearate, propylene glycol stearate SE,PVP, pyridoxine dipalmitate, retinol, retinyl palmitate, rice (oryzasativa) bran oil, RNA, rosemary (rosmarinus officinalis) oil, rose oil,safflower (carthamus tinctorius) oil, sage (salvia officinalis) oil,sandalwood (santalum album) oil, serine, serum protein, sesame (sesamumindicum) oil, shea butter (butyrospermum parkii), silk powder, sodiumchondroitin sulfate, sodium hyaluronate, sodium lactate, sodiumpalmitate, sodium PCA, sodium polyglutamate, soluble collagen, sorbitanlaurate, sorbitan oleate, sorbitan palmitate, sorbitan sesquioleate,sorbitan stearate, sorbitol, soybean (glycine soja) oil, sphingolipids,squalane, squalene, stearamide MEA-stearate, stearic acid, stearoxydimethicone, stearoxytrimethylsilane, stearyl alcohol, stearylglycyrrhetinate, stearyl heptanoate, stearyl stearate, sunflower(helianthus annuus) seed oil, sweet almond (prunus amygdalus dulcis)oil, synthetic beeswax, tocopherol, tocopheryl acetate, tocopheryllinoleate, tribehenin, tridecyl neopentanoate, tridecyl stearate,triethanolamine, tristearin, urea, vegetable oil, water, waxes, wheat(triticum vulgare) germ oil, and ylang ylang (cananga odorata) oil.

c. Antioxidants

Non-limiting examples of antioxidants that can be used with thecompositions of the present invention include acetyl cysteine, ascorbicacid polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanolpectinate, ascorbyl palmitate, ascorbyl stearate, BHA, BHT, t-butylhydroquinone, cysteine, cysteine HCI, diamylhydroquinone,di-t-butylhydroquinone, dicetyl thiodipropionate, dioleyl tocopherylmethylsilanol, disodium ascorbyl sulfate, distearyl thiodipropionate,ditridecyl thiodipropionate, dodecyl gallate, erythorbic acid, esters ofascorbic acid, ethyl ferulate, ferulic acid, gallic acid esters,hydroquinone, isooctyl thioglycolate, kojic acid, magnesium ascorbate,magnesium ascorbyl phosphate, methylsilanol ascorbate, natural botanicalanti-oxidants such as green tea or grape seed extracts,nordihydroguaiaretic acid, octyl gallate, phenylthioglycolic acid,potassium ascorbyl tocopheryl phosphate, potassium sulfite, propylgallate, quinones, rosmarinic acid, sodium ascorbate, sodium bisulfite,sodium erythorbate, sodium metabisulfite, sodium sulfite, superoxidedismutase, sodium thioglycolate, sorbityl furfural, thiodiglycol,thiodiglycolamide, thiodiglycolic acid, thioglycolic acid, thiolacticacid, thiosalicylic acid, tocophereth-5, tocophereth-10, tocophereth-12,tocophereth-18, tocophereth-50, tocopherol, tocophersolan, tocopherylacetate, tocopheryl linoleate, tocopheryl nicotinate, tocopherylsuccinate, and tris(nonylphenyl)phosphite.

d. Structuring Agents

In other non-limiting aspects, the compositions of the present inventioncan include a structuring agent. Structuring agent, in certain aspects,assist in providing rheological characteristics to the composition tocontribute to the composition's stability. In other aspects, structuringagents can also function as an emulsifier or surfactant. Non-limitingexamples of structuring agents include stearic acid, palmitic acid,stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmiticacid, the polyethylene glycol ether of stearyl alcohol having an averageof about 1 to about 21 ethylene oxide units, the polyethylene glycolether of cetyl alcohol having an average of about 1 to about 5 ethyleneoxide units, and mixtures thereof.

e. Emulsifiers

In certain aspects of the present invention, the compositions do notinclude an emulsifier. In other aspects, however, the compositions caninclude one or more emulsifiers. Emulsifiers can reduce the interfacialtension between phases and improve the formulation and stability of anemulsion. The emulsifiers can be nonionic, cationic, anionic, andzwitterionic emulsifiers (See McCutcheon's (1986); U.S. Pat. Nos.5,011,681; 4,421,769; 3,755,560). Non-limiting examples include estersof glycerin, esters of propylene glycol, fatty acid esters ofpolyethylene glycol, fatty acid esters of polypropylene glycol, estersof sorbitol, esters of sorbitan anhydrides, carboxylic acid copolymers,esters and ethers of glucose, ethoxylated ethers, ethoxylated alcohols,alkyl phosphates, polyoxyethylene fatty ether phosphates, fatty acidamides, acyl lactylates, soaps, TEA stearate, DEA oleth-3 phosphate,polyethylene glycol 20 sorbitan monolaurate (polysorbate 20),polyethylene glycol 5 soya sterol, steareth-2, steareth-20, steareth-21,ceteareth-20, PPG-2 methyl glucose ether distearate, ceteth-10,polysorbate 80, cetyl phosphate, potassium cetyl phosphate,diethanolamine cetyl phosphate, polysorbate 60, glyceryl stearate,PEG-100 stearate, and mixtures thereof.

f. Silicone Containing Compounds

In non-limiting aspects, silicone containing compounds include anymember of a family of polymeric products whose molecular backbone ismade up of alternating silicon and oxygen atoms with side groupsattached to the silicon atoms. By varying the —Si—O— chain lengths, sidegroups, and crosslinking, silicones can be synthesized into a widevariety of materials. They can vary in consistency from liquid to gel tosolids.

The silicone containing compounds that can be used in the context of thepresent invention include those described in this specification or thoseknown to a person of ordinary skill in the art. Non-limiting examplesinclude silicone oils (e.g., volatile and non-volatile oils), gels, andsolids. In certain aspects, the silicon containing compounds includes asilicone oils such as a polyorganosiloxane. Non-limiting examples ofpolyorganosiloxanes include dimethicone, cyclomethicone,polysilicone-11, phenyl trimethicone, trimethylsilylamodimethicone,stearoxytrimethylsilane, or mixtures of these and other organosiloxanematerials in any given ratio in order to achieve the desired consistencyand application characteristics depending upon the intended application(e.g., to a particular area such as the skin, hair, or eyes). A“volatile silicone oil” includes a silicone oil have a low heat ofvaporization, i.e. normally less than about 50 cal per gram of siliconeoil. Non-limiting examples of volatile silicone oils include:cyclomethicones such as Dow Corning 344 Fluid, Dow Corning 345 Fluid,Dow Corning 244 Fluid, and Dow Corning 245 Fluid, Volatile Silicon 7207(Union Carbide Corp., Danbury, Conn.); low viscosity dimethicones, i.e.dimethicones having a viscosity of about 50 cst or less (e.g.,dimethicones such as Dow Corning 200-0.5 cst Fluid). The Dow CorningFluids are available from Dow Corning Corporation, Midland, Mich.Cyclomethicone and dimethicone are described in the Third Edition of theCTFA Cosmetic Ingredient Dictionary (incorporated by reference) ascyclic dimethyl polysiloxane compounds and a mixture of fully methylatedlinear siloxane polymers end-blocked with trimethylsiloxy units,respectively. Other non-limiting volatile silicone oils that can be usedin the context of the present invention include those available fromGeneral Electric Co., Silicone Products Div., Waterford, N.Y. and SWSSilicones Div. of Stauffer Chemical Co., Adrian, Mich.

g. Essential Oils

Essential oils include oils derived from herbs, flowers, trees, andother plants. Such oils are typically present as tiny droplets betweenthe plant's cells, and can be extracted by several method known to thoseof skill in the art (e.g., steam distilled, enfleurage (i.e., extractionby using fat), maceration, solvent extraction, or mechanical pressing).When these types of oils are exposed to air they tend to evaporate(i.e., a volatile oil). As a result, many essential oils are colorless,but with age they can oxidize and become darker. Essential oils areinsoluble in water and are soluble in alcohol, ether, fixed oils(vegetal), and other organic solvents. Typical physical characteristicsfound in essential oils include boiling points that vary from about 160°to 240° C. and densities ranging from about 0.759 to about 1.096.

Essential oils typically are named by the plant from which the oil isfound. For example, rose oil or peppermint oil are derived from rose orpeppermint plants, respectively. Non-limiting examples of essential oilsthat can be used in the context of the present invention include sesameoil, macadamia nut oil, tea tree oil, evening primrose oil, Spanish sageoil, Spanish rosemary oil, coriander oil, thyme oil, pimento berriesoil, rose oil, anise oil, balsam oil, bergamot oil, rosewood oil, cedaroil, chamomile oil, sage oil, clary sage oil, clove oil, cypress oil,eucalyptus oil, fennel oil, sea fennel oil, frankincense oil, geraniumoil, ginger oil, grapefruit oil, jasmine oil, juniper oil, lavender oil,lemon oil, lemongrass oil, lime oil, mandarin oil, marjoram oil, myrrhoil, neroli oil, orange oil, patchouli oil, pepper oil, black pepperoil, petitgrain oil, pine oil, rose otto oil, rosemary oil, sandalwoodoil, spearmint oil, spikenard oil, vetiver oil, wintergreen oil, orylang ylang. Other essential oils known to those of skill in the art arealso contemplated as being useful within the context of the presentinvention.

h. Thickening Agents

Thickening agents, including thickener or gelling agents, includesubstances which that can increase the viscosity of a composition.Thickeners includes those that can increase the viscosity of acomposition without substantially modifying the efficacy of the activeingredient within the composition. Thickeners can also increase thestability of the compositions of the present invention. In certainaspects of the present invention, thickeners include hydrogenatedpolyisobutene or trihydroxystearin, or a mixture of both.

Non-limiting examples of additional thickening agents that can be usedin the context of the present invention include carboxylic acidpolymers, crosslinked polyacrylate polymers, polyacrylamide polymers,polysaccharides, and gums. Examples of carboxylic acid polymers includecrosslinked compounds containing one or more monomers derived fromacrylic acid, substituted acrylic acids, and salts and esters of theseacrylic acids and the substituted acrylic acids, wherein thecrosslinking agent contains two or more carbon-carbon double bonds andis derived from a polyhydric alcohol (see U.S. Pat. Nos. 5,087,445;4,509,949; 2,798,053; CTFA International Cosmetic Ingredient Dictionary,Fourth edition, 1991, pp. 12 and 80). Examples of commercially availablecarboxylic acid polymers include carbomers, which are homopolymers ofacrylic acid crosslinked with allyl ethers of sucrose or pentaerytritol(e.g., Carbopol™ 900 series from B. F. Goodrich).

Non-limiting examples of crosslinked polyacrylate polymers includecationic and nonionic polymers. Examples are described in U.S. Pat. Nos.5,100,660 ; 4,849,484; 4,835,206; 4,628,078; 4,599,379).

Non-limiting examples of polyacrylamide polymers (including nonionicpolyacrylamide polymers including substituted branched or unbranchedpolymers) include polyacrylamide, isoparaffin and laureth-7, multi-blockcopolymers of acrylamides and substituted acrylamides with acrylic acidsand substituted acrylic acids.

Non-limiting examples of polysaccharides include cellulose,carboxymethyl hydroxyethylcellulose, cellulose acetate propionatecarboxylate, hydroxyethylcellulose, hydroxyethyl ethylcellulose,hydroxypropylcellulose, hydroxypropyl methylcellulose, methylhydroxyethylcellulose, microcrystalline cellulose, sodium cellulosesulfate, and mixtures thereof. Another example is an alkyl substitutedcellulose where the hydroxy groups of the cellulose polymer ishydroxyalkylated (preferably hydroxy ethylated or hydroxypropylated) toform a hydroxyalkylated cellulose which is then further modified with aC₁₀ -C₃₀ straight chain or branched chain alkyl group through an etherlinkage. Typically these polymers are ethers of C₁₀-C₃₀ straight orbranched chain alcohols with hydroxyalkylcelluloses. Other usefulpolysaccharides include scleroglucans comprising a linear chain of (1-3)linked glucose units with a (1-6) linked glucose every three unit.

Non-limiting examples of gums that can be used with the presentinvention include acacia, agar, algin, alginic acid, ammonium alginate,amylopectin, calcium alginate, calcium carrageenan, carnitine,carrageenan, dextrin, gelatin, gellan gum, guar gum, guarhydroxypropyltrimonium chloride, hectorite, hyaluroinic acid, hydratedsilica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp,locust bean gum, natto gum, potassium alginate, potassium carrageenan,propylene glycol alginate, sclerotium gum, sodium carboyxmethyl dextran,sodium carrageenan, tragacanth gum, xanthan gum, and mixtures thereof.

i. Preservatives

Non-limiting examples of preservatives that can be used in the contextof the present invention include quaternary ammonium preservatives suchas polyquaternium-1 and benzalkonium halides (e.g., benzalkoniumchloride (“BAC”) and benzalkonium bromide), parabens (e.g.,methylparabens and propylparabens), phenoxyethanol, benzyl alcohol,chlorobutanol, phenol, sorbic acid, thimerosal or combinations thereof.

2. Pharmaceutical Ingredients

Pharmaceutical active agents are also contemplated as being useful withthe compositions of the present invention. Non-limiting examples ofpharmaceutical active agents include anti-acne agents, agents used totreat rosacea, analgesics, anesthetics, anorectals, antihistamines,anti-inflammatory agents including non-steroidal anti-inflammatorydrugs, antibiotics, antifungals, antivirals, antimicrobials, anti-canceractives, scabicides, pediculicides, antineoplastics, antiperspirants,antipruritics, antipsoriatic agents, antiseborrheic agents, biologicallyactive proteins and peptides, burn treatment agents, cauterizing agents,depigmenting agents, depilatories, diaper rash treatment agents,enzymes, hair growth stimulants, hair growth retardants including DFMOand its salts and analogs, hemostatics, kerotolytics, canker soretreatment agents, cold sore treatment agents, dental and periodontaltreatment agents, photosensitizing actives, skin protectant/barrieragents, steroids including hormones and corticosteroids, sunburntreatment agents, sunscreens, transdermal actives, nasal actives,vaginal actives, wart treatment agents, wound treatment agents, woundhealing agents, etc.

I. Kits

Kits are also contemplated as being used in certain aspects of thepresent invention. For instance, compositions of the present inventioncan be included in a kit. A kit can include a container. Containers caninclude a bottle, a metal tube, a laminate tube, a plastic tube, adispenser, a pressurized container, a barrier container, a package, acompartment, a lipstick container, a compact container, cosmetic pansthat can hold cosmetic compositions, or other types of containers suchas injection or blow-molded plastic containers into which thedispersions or compositions or desired bottles, dispensers, or packagesare retained. The kit and/or container can include indicia on itssurface. The indicia, for example, can be a word, a phrase, anabbreviation, a picture, or a symbol.

The containers can dispense a pre-determined amount of the composition.In other embodiments, the container can be squeezed (e.g., metal,laminate, or plastic tube) to dispense a desired amount of thecomposition. The composition can be dispensed as a spray, an aerosol, aliquid, a fluid, or a semi-solid. The containers can have spray, pump,or squeeze mechanisms. A kit can also include instructions for employingthe kit components as well the use of any other compositions included inthe container. Instructions can include an explanation of how to apply,use, and maintain the compositions.

EXAMPLES

The following examples are included to demonstrate certain non-limitingaspects of the invention. It should be appreciated by those of skill inthe art that the techniques disclosed in the examples which followrepresent techniques discovered by the inventor to function well in thepractice of the invention. However, those of skill in the art should, inlight of the present disclosure, appreciate that many changes can bemade in the specific embodiments which are disclosed and still obtain alike or similar result without departing from the spirit and scope ofthe invention.

Example 1 Formulations

The Tables 1-2 compositions are non-limiting compositions that can beused in the context of the present invention.

TABLE 1* Ingredient % Concentration (by weight) Phase A Water q.sXanthum gum 0.1 M-paraben 0.15 P-paraben 0.1 Citric acid 0.01 Phase BCetyl alcohol 4.0 Glyceryl stearate + PEG 100 4.0 Octyl palmitate 4.0Dimethicone 1.0 Tocopheryl acetate 0.2 Phase C Combination(s)** 1 to 20*Sprinkle Xanthum gum in water and mix for 10 min. Subsequently, add allingredients in phase A and heat to 70-75° C. Add all items in phase B toseparate beaker and heat to 70-75° C. Mix phases A and B at 70-75° C.Continue mixing and allow composition to cool to 30° C. Subsequently,add phase C ingredient while mixing. **The combination of ingredientsdisclosed throughout this specification can be used. For instance, thecombination of Centella asiatica stem cells, tetradecylaminobutyroylvalylamino butyric urea trifluoroacetate, and tripeptide-1can be used. Alternatively, the combination of Centella asiatica stemcells, Alpinia galanga leaf extract, and tripeptide-1 can be used.

TABLE 2* Ingredient % Concentration (by weight) Phase A Water q.sM-paraben 0.2 P-paraben 0.1 Na2 EDTA 0.1 Shea butter 4.5 Petrolatum 4.5Glycerin 4.0 Propylene Glycol 2.0 Finsolve TN 2.0 Phase B Sepigel 3052.0 Phase C Combinations(s)** 1 to 20 *Add ingredients in phase A tobeaker and heat to 70-75° C. while mixing. Subsequently, add the phase Bingredient with phase A and cool to 30° C. with mixing. Subsequently,add phase C ingredient while mixing. **The combination of ingredientsdisclosed throughout this specification can be used. For instance, thecombination of Centella asiatica stem cells, tetradecylaminobutyroylvalylamino butyric urea trifluoroacetate, and tripeptide-1can be used. Alternatively, the combination of Centella asiatica stemcells, Alpinia galanga leaf extract, and tripeptide-1 can be used.

Example 2 In vitro Data

Tripeptide-1 (Kollaren from Unipex/Lucas Meyer): Staining of culturedhuman fibroblasts using immunofluorescent antibodies directed againstdermal matrix proteins demonstrate a 305% and 105% increase in collagenI and collagen III, respectively, compared to untreated controls.Additional immunofluorescence studies demonstrate a 15% increase inelastin fibers. Tripeptide-1 was also found to activate the synthesis oflaminin and fibronectin by increasing secretion of fibronectin andlaminin by 105% and 85%, respectively, compared to untreated controls.Further in vitro studies using cultured human dermal fibroblastsdemonstrated that tripeptide-1 also increased the production ofhyaluronic acid secretion by 118% compared to an untreated control.

Centella asiatica stem cells (Centella Asiatica Stems G from RicercheBiotecnologiche): Enzymatic activity assays demonstrated that stem cellsderived from Centella asiatica cell cultures (CAS) inhibits the activityof hyaluronidase up to 90% compared to untreated controls.

Tetradecyl aminobutyroylvalylamino butyric urea trifluoroacetate(Syn-Hycan from Pentapharm/DSM): In vitro studies using cultured humandermal fibroblasts demonstrated that tetradecyl aminobutyroylvalylaminobutyric urea trifluoroacetate increased the production of hyaluronicacid secretion by 64.2% compared to an untreated control.

The combination of these ingredients were tested in various topical skinformulations (See Example 3) to treat skin. These data suggest asynergistic effect, as each of the ingredients individually are directedto various pathways (e.g, laminin and fibronectin production, inhibitionof hyaluronidase, to increased hyaluronic acid production) whereas thecombination results in an effective way to improve the appearance agingskin by firming the skin while also adding volume to the skin.

Example 3 In vivo Data

As noted above, the combination of tripeptide-1 (Kollaren fromUnipex/Lucas Meyer), Centella asiatica stem cells (Centella AsiaticaStems G from Ricerche Biotecnologiche), and tetradecylaminobutyroylvalylamino butyric urea trifluoroacetate (Syn-Hycan fromPentapharm/DSM) was tested on skin at various levels in variousdermatologically acceptable vehicles. The following includes dataconcerning these tests.

A cleansing formulation having 0.0001% by weight Centella asiatica stemcells, 0.00001% by weight tetradecyl aminobutyroylvalylamino butyricurea trifluoroacetate, and 0.000001% by weight of tripeptide-1 wastested by 193 women, using the cleanser twice daily for 1-week. Theresults of the study were: 86% of the women said the cleanser maintainedskin moisture balance; 87% of the women said the cleanser renewed theskin's radiance; 89% of the women said the cleanser left the skinfeeling supple; and 90% of the women said the cleanser left the skinfeeling pampered.

A serum formulation having 0.25% by weight Centella asiatica stem cells,0.5% by weight tetradecyl aminobutyroylvalylamino butyric ureatrifluoroacetate, and 0.5% by weight of tripeptide-1 was tested by 191women, using the serum twice daily for 4-weeks: 74% of the women saidthe skin appears tighter; 67% of the women said the youthful volume andvibrancy of the skin are restored; 73% of the women said the serumsoftens the look of lines and wrinkles on the neck; and 79% of womensaid that it helped the skin look more youthful all day. After a 12-weekclinical study, in which 45 women used the serum twice daily, 89% of thewomen saw an increase in skin firmness.

A day cream formulation having 0.25% by weight Centella asiatica stemcells, 0.5% by weight tetradecyl aminobutyroylvalylamino butyric ureatrifluoroacetate, and 0.5% by weight of tripeptide-1 was tested by 181women, using the cream once a day in the morning for 4-weeks: 70% of thewomen said the cream minimized the appearance of deep wrinkles; 74% ofthe women said the cream softened the appearance of crepiness on theneck; 80% of the women said the cream restored youthful cushion to theskin; and 82% of the women said the cream evened the skin tone.

A night cream formulation having 0.05% by weight Centella asiatica stemcells, 0.00055% by weight tetradecyl aminobutyroylvalylamino butyricurea trifluoroacetate, and 0.00005% by weight of tripeptide-1 was testedby 185 women, using the cream once a day in the evening for 4-weeks: 76%of the women said the cream improved the advanced signs of aging; 71% ofthe women said the skin regained firmness; 67% of the women said thejawline area appeared more defined; 81% of the women said the creamrestored a youthful cushion to skin; 86% of the women said the creamevened the skin tone; and 90% of the women said that the cream enhancedthe skin's overall appearance.

An eye cream formulation having 0.1% by weight Centella asiatica stemcells, 0.000001% by weight tetradecyl aminobutyroylvalylamino butyricurea trifluoroacetate, and 0.000055% by weight of tripeptide-1 wastested by 180 women, using the cream twice a day in for 4-weeks: After 1week of use, 81% of women said the cream reduced the look of crepey skinwhile 86% of the women said the cream helped minimize the look ofunder-eye bags and dark circles; after 2 weeks of use, 73% of the womensaid the cream firmed and toned sagging skin around the eyes, 73% of thewomen said that the cream minimized the appearance of deep wrinkles, and71% of the women indicated that the cream restored a youthful lift tothe skin; and after 4 weeks of use, 85% of the women said the creamhelped repair the skin's appearance while 67% of the women said that thecream reduced the appearance of droopy eyelids. FIG. 1 provides a beforeand after picture of skin around the eyes after 4 weeks of use, twicedaily, of one subject, which illustrates a noticeable decrease in theappearance of wrinkling and crepiness on the upper eyelid and in thecrow's feet area.

A regimen using each of the above mentioned formulations daily (asindicated above) for a period of 12 weeks was tested by 43 women. After12 weeks, 91% of the women indicated that they had less noticeable deeplines and wrinkles, 86% had skin that looked lifted, 98% had lessunder-eye puffiness, 93% had more even skin tone, and 93% had asignificant improvement in overall appearance. Further, 40% of the womenobserved an improvement in skin firmness and 58% saw an improvement inskin elasticity. Also, 86% of the women had a decrease in the appearanceof average wrinkle length, and 81% of the women had a decrease in theappearance of average wrinkle width. Further, 70% of the women showedsigns of lifting along the jawline. FIG. 2 provides a before and afterpicture of skin on an individual's forehead after following the regimenfor 12 weeks. This FIG. 2 illustrates a noticeable decrease in the lookof deep wrinkles (shown with arrows) and fine lines (remaining lines nothighlighted with arrows) across the forehead.

Example 4 In vitro and vivo Data

In this study, tetradecyl aminobutyroylvalylamino butyric ureatrifluoroacetate (Syn-Hycan from Pentapharm/DSM) was replaced withAlpinia galanga leaf extract (Hyalufix™ GL from BASF). Therefore, thecombination of tripeptide-1 (Kollaren from Unipex/Lucas Meyer), Centellaasiatica stem cells (Centella Asiatica Stems G from RicercheBiotecnologiche), and Alpinia galanga leaf extract (Hyalufix™ GL fromBASF) was tested on skin at various levels in various dermatologicallyacceptable vehicles. The following includes data concerning these tests.Further, an in vitro assay was performed on Alpinia galanga leaf extractusing cultured human dermal fibroblasts. This in vitro assaydemonstrated the effectiveness of Alpinia galanga leaf extract toincrease the production of hyaluronic acid in said fibroblasts, whilealso increasing collagen and laminin production too.

A serum formulation having 0.05% by weight Centella asiatica stem cells,0.025% by weight Alpinia galanga leaf extract, and 0.00005% by weight oftripeptide-1 was tested by a population of women, using the serum twicedaily for 4-weeks. After 1 week of use, 80% of the women had anoticeable lifting sensation, while 88% had increased skin moisture.After 2 weeks of use, 78% of women said their jawline area appearedlifted, 81% said the serum helped define and perfect facial contours,82% noticed firmed and tightened skin that was previously sagging, and79% of women said the serum reversed the loss of cushion in the skin.After 4 weeks, 82% of the women noticed a lifting of the skin that laststhroughout the day, while 79% indicated that the neck area appearedfirmed.

An eye cream formulation having 0.002% by weight Centella asiatica stemcells and 0.00005% by weight of tripeptide-1 (no Alpinia galanga leafextract was used) was tested by a population of women, using the creamtwice daily for 4-weeks. After 1 week of use, 79% of the women said theeye area appeared more lifted, 78% said the under eye puffiness wasreduced, and 75% said the crow's feet were minimized. After 2 weeks ofuse, 83% said dark circles were minimized, 80% said the cream firmedsagging skin around the eyes, and 79% said that the cream minimized theappearance of deep lines. After 4 weeks of use, 81% said that theeyelids had a less hooded appearance, 76% said the eye area appeareddramatically younger, 94% said that the cream helped repair the skin'sappearance, and 86% indicated that the skin regained a youthfulresilience.

Example 5 Assays

Additional assays that can be used to determine the efficacy of any oneof the ingredients or any combination of ingredients or compositionshaving said combination of ingredients disclosed throughout thespecification and claims can be determined by methods known to those ofordinary skill in the art. The following are non-limiting assays thatcan be used in the context of the present invention. It should berecognized that other testing procedures can be used, including, forexample, objective and subjective procedures.

B16 Pigmentation Assay: Melanogenesis is the process by whichmelanocytes produce melanin, a naturally produced pigment that impartscolor to skin, hair, and eyes. Inhibiting melanogenesis is beneficial toprevent skin darkening and lighten dark spots associated with aging.This bioassay utilizes B16-F1 melanocytes (ATCC), an immortalized mousemelanoma cell line, to analyze the effect of compounds on melanogenesis.The endpoint of this assay is a spectrophotometric measurement ofmelanin production and cellular viability.

B16-F1 melanocytes, can be cultivated in standard DMEM growth mediumwith 10% fetal bovine serum (Mediatech) at 37° C. in 10% CO₂ and thentreated with any one of the active ingredients, combination ofingredients, or compositions having said combinations disclosed in thespecification for 6 days. Following incubation, melanin secretion wasmeasured by absorbance at 405 nm and cellular viability was quantified.

Collagen Stimulation Assay: Collagen is an extracellular matrix proteincritical for skin structure. Increased synthesis of collagen helpsimprove skin firmness and elasticity. This bioassay can be used toexamine the effect of any one of the active ingredients, combination ofingredients, or compositions having said combinations disclosed in thespecification on the production of procollagen peptide (a precursor tocollagen) by human epidermal fibroblasts. The endpoint of this assay isa spectrophotometric measurement that reflects the presence ofprocollagen peptide and cellular viability. The assay employs thequantitative sandwich enzyme immunoassay technique whereby a monoclonalantibody specific for procollagen peptide has been pre-coated onto amicroplate. Standards and samples can be pipetted into the wells and anyprocollagen peptide □ present is bound by the immobilized antibody.After washing away any unbound substances, an enzyme-linked polyclonalantibody specific for procollagen peptide can be added to the wells.Following a wash to remove any unbound antibody-enzyme reagent, asubstrate solution can be added to the wells and color develops inproportion to the amount of procollagen peptide bound in the initialstep using a microplate reader for detection at 450 nm. The colordevelopment can be stopped and the intensity of the color can bemeasured. Subconfluent normal human adult epidermal fibroblasts (CascadeBiologics) cultivated in standard DMEM growth medium with 10% fetalbovine serum (Mediatech) at 37° C. in 10% CO₂, can be treated with eachof the combination of ingredients or compositions having saidcombinations disclosed in the specification for 3 days. Followingincubation, cell culture medium can be collected and the amount ofprocollagen peptide secretion quantified using a sandwich enzyme linkedimmuno-sorbant assay (ELISA) from Takara (#MK101).

Tumor Necrosis Factor Alpha (TNF-α) Assay: The prototype ligand of theTNF superfamily, TNF-α, is a pleiotropic cytokine that plays a centralrole in inflammation. Increase in its expression is associated with anup regulation in pro-inflammatory activity. This bioassay can be used toanalyze the effect of any one of the active ingredients, combination ofingredients, or compositions having said combinations disclosed in thespecification on the production of TNF-α by human epidermalkeratinocytes. The endpoint of this assay can be a spectrophotometricmeasurement that reflects the presence of TNF-α and cellular viability.The assay employs the quantitative sandwich enzyme immunoassay techniquewhereby a monoclonal antibody specific for TNF-α has been pre-coatedonto a microplate. Standards and samples can be pipetted into the wellsand any TNF-α present is bound by the immobilized antibody. Afterwashing away any unbound substances, an enzyme-linked polyclonalantibody specific for TNF-α can be added to the wells. Following a washto remove any unbound antibody-enzyme reagent, a substrate solution canbe added to the wells and color develops in proportion to the amount ofTNF-α bound in the initial step using a microplate reader for detectionat 450 nm. The color development can be stopped and the intensity of thecolor can be measured. Subconfluent normal human adult keratinocytes(Cascade Biologics) cultivated in EpiLife standard growth medium(Cascade Biologics) at 37° C. in 5% CO₂, can be treated with phorbol12-myristate 13-acetate (PMA, 10 ng/ml, Sigma Chemical, #P1585-1MG) andany one of the active ingredients, combination of ingredients, orcompositions having said combinations disclosed in the specification for6 hours. PMA has been shown to cause a dramatic increase in TNF-αsecretion which peaks at 6 hours after treatment. Following incubation,cell culture medium can be collected and the amount of TNF-α secretionquantified using a sandwich enzyme linked immuno-sorbant assay (ELISA)from R&D Systems (#DTA00C).

Antioxidant (AO) assay: An in vitro bioassay that measures the totalanti-oxidant capacity of any one of the ingredients, combination ofingredients, or compositions having said combinations disclosed in thespecification. The assay relies on the ability of antioxidants in thesample to inhibit the oxidation of ABTS®(2,2′-azino-di-[3-ethylbenzthiazoline sulphonate]) to ABTS®·+ bymetmyoglobin. The antioxidant system of living organisms includesenzymes such as superoxide dismutase, catalase, and glutathioneperoxidase; macromolecules such as albumin, ceruloplasmin, and ferritin;and an array of small molecules, including ascorbic acid, α-tocopherol,β-carotene, reduced glutathione, uric acid, and bilirubin. The sum ofendogenous and food-derived antioxidants represents the totalantioxidant activity of the extracellular fluid. Cooperation of all thedifferent antioxidants provides greater protection against attack byreactive oxygen or nitrogen radicals, than any single compound alone.Thus, the overall antioxidant capacity may give more relevant biologicalinformation compared to that obtained by the measurement of individualcomponents, as it considers the cumulative effect of all antioxidantspresent in plasma and body fluids. The capacity of the antioxidants inthe sample to prevent ABTS oxidation is compared with that of Trolox, awater-soluble tocopherol analogue, and is quantified as molar Troloxequivalents. Anti-Oxidant capacity kit #709001 from Cayman Chemical (AnnArbor, Mich. USA) can be used as an in vitro bioassay to measure thetotal anti-oxidant capacity of each of any one of the activeingredients, combination of ingredients, or compositions having saidcombinations disclosed in the specification. The protocol can befollowed according to manufacturer recommendations. The assay relied onantioxidants in the sample to inhibit the oxidation of ABTS®(2,2′-azino-di-[3-ethylbenzthiazoline sulphonate]) to ABTS®·+ bymetmyoglobin. The capacity of the antioxidants in the sample to preventABTS oxidation can be compared with that Trolox, a water-solubletocopherol analogue, and was quantified as a molar Trolox equivalent.

ORAC Assay: Oxygen Radical Absorption (or Absorbance) Capacity (ORAC) ofany one of the active ingredients, combination of ingredients, orcompositions having said combinations disclosed in the specification canalso be assayed by measuring the antioxidant activity of suchingredients or compositions. This assay can quantify the degree andlength of time it takes to inhibit the action of an oxidizing agent suchas oxygen radicals that are known to cause damage cells (e.g., skincells). The ORAC value of any one of the active ingredients, combinationof ingredients, or compositions having said combinations disclosed inthe specification can be determined by methods known to those ofordinary skill in the art (see U.S. Publication Nos. 2004/0109905 and2005/0163880; Cao et al. (1993)), all of which are incorporated byreference). In summary, the assay described in Cao et al. (1993)measures the ability of antioxidant compounds in test materials toinhibit the decline of B-phycoerythrm (B-PE) fluorescence that isinduced by a peroxyl radical generator, AAPH.

Mushroom tyrosinase activity assay: In mammalian cells, tyrosinasecatalyzes two steps in the multi-step biosynthesis of melanin pigmentsfrom tyrosine (and from the polymerization of dopachrome). Tyrosinase islocalized in melanocytes and produces melanin (aromatic quinonecompounds) that imparts color to skin, hair, and eyes. Purified mushroomtyrosinase (Sigma) can be incubated with its substrate L-Dopa (Fisher)in the presence or absence of each of the active ingredients, any one ofthe combination of ingredients, or compositions having said combinationsdisclosed in the specification. Pigment formation can be evaluated bycolorimetric plate reading at 490 nm. The percent inhibition of mushroomtyrosinase activity can be calculated compared to non-treated controlsto determine the ability of test ingredients or combinations thereof toinhibit the activity of purified enzyme. Test extract inhibition wascompared with that of kojic acid (Sigma).

Matrix Metalloproteinase Enzyme Activity (MMP3; MMP9) Assay: An in vitromatrix metalloprotease (MMP) inhibition assay. MMPs are extracellularproteases that play a role in many normal and disease states by virtueof their broad substrate specificity. MMP3 substrates include collagens,fibronectins, and laminin; while MMP9 substrates include collagen VII,fibronectins and laminin. Using Colorimetric Drug Discovery kits fromBioMol International for MMP3 (AK-400) and MMP-9 (AK-410), this assay isdesigned to measure protease activity of MMPs using a thiopeptide as achromogenic substrate(Ac-PLG-[2-mercapto-4-methyl-pentanoyl]-LG-OC2H5)5,6. The MMP cleavagesite peptide bond is replaced by a thioester bond in the thiopeptide.Hydrolysis of this bond by an MMP produces a sulfhydryl group, whichreacts with DTNB [5,5′-dithiobis(2-nitrobenzoic acid), Ellman's reagent]to form 2-nitro-5-thiobenzoic acid, which can be detected by itsabsorbance at 412 nm (ε=13,600 M-1 cm-1 at pH 6.0 and above 7). Theactive ingredients, any one of the combination of ingredients, orcompositions having said combinations disclosed in the specification canbe assayed.

Cyclooxygenase (COX) Assay: An in vitro cyclooxygenase-1 and -2 (COX-1,-2) inhibition assay. COX is a bifunctional enzyme exhibiting bothcyclooxygenase and peroxidase activities. The cyclooxygenase activityconverts arachidonic acid to a hydroperoxy endoperoxide (ProstaglandinG2; PGG2) and the peroxidase component reduces the endoperoxide(Prostaglandin H2; PGH2) to the corresponding alcohol, the precursor ofprostaglandins, thromboxanes, and prostacyclins. This COX Inhibitorscreening assay measures the peroxidase component of cyclooxygenases.The peroxidase activity is assayed colorimetrically by monitoring theappearance of oxidized N,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD).This inhibitor screening assay includes both COX-1 and COX-2 enzymes inorder to screen isozyme-specific inhibitors. The Colormetric COX (ovine)Inhibitor screening assay (#760111, Cayman Chemical) can be used toanalyze the effects of each of the active ingredients, any one of thecombination of ingredients, or compositions having said combinationsdisclosed in the specification on the activity of purified cyclooxygnaseenzyme (COX-1 or COX-2). According to manufacturer instructions,purified enzyme, heme and test extracts can be mixed in assay buffer andincubated with shaking for 15 min at room temperature. Followingincubation, arachidonic acid and colorimetric substrate can be added toinitiate the reaction. Color progression can be evaluated bycolorimetric plate reading at 590 nm. The percent inhibition of COX-1 orCOX-2 activity can be calculated compared to non-treated controls todetermine the ability of test extracts to inhibit the activity ofpurified enzyme.

Lipoxygenase (LO) Assay: An in vitro lipoxygenase (LO) inhibition assay.LOs are non-heme iron-containing dioxygenases that catalyze the additionof molecular oxygen to fatty acids. Linoleate and arachidonate are themain substrates for LOs in plants and animals. Arachadonic acid may thenbe converted to hydroxyeicosotrienenoic (HETE) acid derivatives, thatare subsequently converted to leukotirenes, potent inflammatorymediators. This assay provides an accurate and convenient method forscreening lipoxygenase inhibitors by measuring the hydroperoxidesgenerated from the incubation of a lipoxygenase (5-, 12-, or 15-LO) witharachidonic acid. The Colorimetric LO Inhibitor screening kit (#760700,Cayman Chemical) can be used to determine the ability of each of theactive ingredients, any one of the combination of ingredients, orcompositions having said combinations disclosed in the specification toinhibit enzyme activity. Purified 15-lipoxygenase and test ingredientscan be mixed in assay buffer and incubated with shaking for 10 min atroom temperature. Following incubation, arachidonic acid can be added toinitiate the reaction and mixtures incubated for an additional 10 min atroom temperature. Colorimetric substrate can be added to terminatecatalysis and color progression was evaluated by fluorescence platereading at 490 nm. The percent inhibition of lipoxyganse activity can becalculated compared to non-treated controls to determine the ability ofeach of the active ingredients, any one of the combination ofingredients, or compositions having said combinations disclosed in thespecification to inhibit the activity of purified enzyme.

Elastase Assay: EnzChek® Elastase Assay (Kit #E-12056) from MolecularProbes (Eugene, Oreg. USA) can be used as an in vitro enzyme inhibitionassay for measuring inhibition of elastase activity for each of theactive ingredients, any one of the combination of ingredients, orcompositions having said combinations disclosed in the specification.The EnzChek kit contains soluble bovine neck ligament elastin that canbe labeled with dye such that the conjugate's fluorescence can bequenched. The non-fluorescent substrate can be digested by elastase orother proteases to yield highly fluorescent fragments. The resultingincrease in fluorescence can be monitored with a fluorescence microplatereader. Digestion products from the elastin substrate have absorptionmaxima at ˜505 nm and fluorescence emission maxima at ˜515 nm. Thepeptide, chloromethyl ketone, can be used as a selective, collectiveinhibitor of elastase when utilizing the EnzChek Elastase Assay Kit forscreening for elastase inhibitors.

Oil Control Assay: An assay to measure reduction of sebum secretion fromsebaceous glands and/or reduction of sebum production from sebaceousglands can be assayed by using standard techniques known to those havingordinary skill in the art. In one instance, the forehead can be used.Each of the active ingredients, any one of the combination ofingredients, or compositions having said combinations disclosed in thespecification can be applied to one portion of the forehead once ortwice daily for a set period of days (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, or more days), while another portion of the foreheadis not treated with the composition. After the set period of daysexpires, then sebum secretion can be assayed by application of fineblotting paper to the treated and untreated forehead skin. This is doneby first removing any sebum from the treated and untreated areas withmoist and dry cloths. Blotting paper can then be applied to the treatedand untreated areas of the forehead, and an elastic band can be placedaround the forehead to gently press the blotting paper onto the skin.After 2 hours the blotting papers can be removed, allowed to dry andthen transilluminated. Darker blotting paper correlates with more sebumsecretion (or lighter blotting paper correlates with reduced sebumsecretion.

Erythema Assay: An assay to measure the reduction of skin redness can beevaluated using a Minolta Chromometer. Skin erythema may be induced byapplying a 0.2% solution of sodium dodecyl sulfate on the forearm of asubject. The area is protected by an occlusive patch for 24 hrs. After24 hrs, the patch is removed and the irritation-induced redness can beassessed using the a* values of the Minolta Chroma Meter. The a* valuemeasures changes in skin color in the red region. Immediately afterreading, the area is treated with the active ingredients, any one of thecombination of ingredients, or compositions having said combinationsdisclosed in the specification. Repeat measurements can be taken atregular intervals to determine the formula's ability to reduce rednessand irritation.

Skin Moisture/Hydration Assay: Skin moisture/hydration benefits can bemeasured by using impedance measurements with the Nova Dermal PhaseMeter. The impedance meter measures changes in skin moisture content.The outer layer of the skin has distinct electrical properties. Whenskin is dry it conducts electricity very poorly. As it becomes morehydrated increasing conductivity results. Consequently, changes in skinimpedance (related to conductivity) can be used to assess changes inskin hydration. The unit can be calibrated according to instrumentinstructions for each testing day. A notation of temperature andrelative humidity can also be made. Subjects can be evaluated asfollows: prior to measurement they can equilibrate in a room withdefined humidity (e.g., 30-50%) and temperature (e.g., 68-72° C.). Threeseparate impedance readings can be taken on each side of the face,recorded, and averaged. The T5 setting can be used on the impedancemeter which averages the impedance values of every five secondsapplication to the face. Changes can be reported with statisticalvariance and significance. Each of the active ingredients, any one ofthe combination of ingredients, or compositions having said combinationsdisclosed in the specification can be assayed according to this process.

Skin Clarity and Reduction in Freckles and Age Spots Assay: Skin clarityand the reduction in freckles and age spots can be evaluated using aMinolta Chromometer. Changes in skin color can be assessed to determineirritation potential due to product treatment using the a* values of theMinolta Chroma Meter. The a* value measures changes in skin color in thered region. This is used to determine whether each of the activeingredients, any one of the combination of ingredients, or compositionshaving said combinations disclosed in the specification is inducingirritation. The measurements can be made on each side of the face andaveraged, as left and right facial values. Skin clarity can also bemeasured using the Minolta Meter. The measurement is a combination ofthe a*, b, and L values of the Minolta Meter and is related to skinbrightness, and correlates well with skin smoothness and hydration. Skinreading is taken as above. In one non-limiting aspect, skin clarity canbe described as L/C where C is chroma and is defined as (a²+b²)^(1/2).

Skin Dryness, Surface Fine Lines, Skin Smoothness, and Skin Tone Assay:Skin dryness, surface fine lines, skin smoothness, and skin tone can beevaluated with clinical grading techniques. For example, clinicalgrading of skin dryness can be determined by a five point standardKligman Scale: (0) skin is soft and moist; (1) skin appears normal withno visible dryness; (2) skin feels slightly dry to the touch with novisible flaking; (3) skin feels dry, tough, and has a whitish appearancewith some scaling; and (4) skin feels very dry, rough, and has a whitishappearance with scaling. Evaluations can be made independently by twoclinicians and averaged.

Clinical Grading of Skin Tone Assay: Clinical grading of skin tone canbe performed via a ten point analog numerical scale: (10) even skin ofuniform, pinkish brown color. No dark, erythremic, or scaly patches uponexamination with a hand held magnifying lens. Microtexture of the skinvery uniform upon touch; (7) even skin tone observed withoutmagnification. No scaly areas, but slight discolorations either due topigmentation or erythema. No discolorations more than 1 cm in diameter;(4) both skin discoloration and uneven texture easily noticeable. Slightscaliness. Skin rough to the touch in some areas; and (1) uneven skincoloration and texture. Numerous areas of scaliness and discoloration,either hypopigmented, erythremic or dark spots. Large areas of unevencolor more than 1 cm in diameter. Evaluations were made independently bytwo clinicians and averaged.

Clinical Grading of Skin Smoothness Assay: Clinical grading of skinsmoothness can be analyzed via a ten point analog numerical scale: (10)smooth, skin is moist and glistening, no resistance upon dragging fingeracross surface; (7) somewhat smooth, slight resistance; (4) rough,visibly altered, friction upon rubbing; and (1) rough, flaky, unevensurface. Evaluations were made independently by two clinicians andaveraged.

Skin Smoothness and Wrinkle Reduction Assay With Methods Disclosed inPackman et al. (1978): Skin smoothness and wrinkle reduction can also beassessed visually by using the methods disclosed in Packman et al.(1978). For example, at each subject visit, the depth, shallowness andthe total number of superficial facial lines (SFLs) of each subject canbe carefully scored and recorded. A numerical score was obtained bymultiplying a number factor times a depth/width/length factor. Scoresare obtained for the eye area and mouth area (left and right sides) andadded together as the total wrinkle score.

Skin Firmness Assay with a Hargens Ballistometer: Skin firmness can bemeasured using a Hargens ballistometer, a device that evaluates theelasticity and firmness of the skin by dropping a small body onto theskin and recording its first two rebound peaks. The ballistometry is asmall lightweight probe with a relatively blunt tip (4 square mm-contactarea) was used. The probe penetrates slightly into the skin and resultsin measurements that are dependent upon the properties of the outerlayers of the skin, including the stratum corneum and outer epidermisand some of the dermal layers.

Skin Softness/Suppleness Assay with a Gas Bearing Electrodynamometer:Skin softness/suppleness can be evaluated using the Gas BearingElectrodynamometer, an instrument that measures the stress/strainproperties of the skin. The viscoelastic properties of skin correlatewith skin moisturization. Measurements can be obtained on thepredetermined site on the cheek area by attaching the probe to the skinsurface with double-stick tape. A force of approximately 3.5 gm can beapplied parallel to the skin surface and the skin displacement isaccurately measured. Skin suppleness can then be calculated and isexpressed as DSR (Dynamic Spring Rate in gm/mm).

Appearance of Lines and Wrinkles Assay with Replicas: The appearance oflines and wrinkles on the skin can be evaluated using replicas, which isthe impression of the skin's surface. Silicone rubber like material canbe used. The replica can be analyzed by image analysis. Changes in thevisibility of lines and wrinkles can be objectively quantified via thetaking of silicon replicas form the subjects' face and analyzing thereplicas image using a computer image analysis system. Replicas can betaken from the eye area and the neck area, and photographed with adigital camera using a low angle incidence lighting. The digital imagescan be analyzed with an image processing program and are of the replicascovered by wrinkles or fine lines was determined.

Surface Contour of the Skin Assay with a Profilometer/Stylus Method: Thesurface contour of the skin can be measured by using theprofilometer/Stylus method. This includes either shining a light ordragging a stylus across the replica surface. The vertical displacementof the stylus can be fed into a computer via a distance transducer, andafter scanning a fixed length of replica a cross-sectional analysis ofskin profile can be generated as a two-dimensional curve. This scan canbe repeated any number of times along a fix axis to generate a simulated3-D picture of the skin. Ten random sections of the replicas using thestylus technique can be obtained and combined to generate averagevalues. The values of interest include Ra which is the arithmetic meanof all roughness (height) values computed by integrating the profileheight relative to the mean profile height. Rt which is the maximumvertical distance between the highest peak and lowest trough, and Rzwhich is the mean peak amplitude minus the mean peak height. Values aregiven as a calibrated value in mm. Equipment should be standardizedprior to each use by scanning metal standards of know values. Ra Valuecan be computed by the following equation: R_(a) =Standardize roughness;l_(m)=the traverse (scan) length; and y=the absolute value of thelocation of the profile relative to the mean profile height (x-axis).

MELANODERM™ Assay: In other non-limiting aspects, the efficacy of eachof the active ingredients, any one of the combination of ingredients, orcompositions having said combinations disclosed in the specificationcompositions can be evaluated by using a skin analog, such as, forexample, MELANODERM™. Melanocytes, one of the cells in the skin analog,stain positively when exposed to L-dihydroxyphenyl alanine (L-DOPA), aprecursor of melanin. The skin analog, MELANODERM™, can be treated witha variety of bases containing each of the active ingredients, any one ofthe combination of ingredients, or compositions having said combinationsdisclosed in the specification or with the base alone as a control.Alternatively, an untreated sample of the skin analog can be used as acontrol.

All of the skin-active ingredients, compositions, or methods disclosedand claimed in this specification can be made and executed without undueexperimentation in light of the present disclosure. While theskin-active ingredients, compositions, or methods of this invention havebeen described in terms of particular embodiments, it will be apparentto those of skill in the art that variations may be applied to theskin-active ingredients, compositions, or methods and in the steps or inthe sequence of steps of the method described herein without departingfrom the concept, spirit and scope of the invention.

1. A method for reducing hyaluronidase activity and promoting hyaluronicacid production in skin comprising topically applying to skin in needthereof a composition comprising: (a) an effective amount of Centellaasiatica stem cells to reduce hyaluronidase activity in skin; (b) aneffective amount of tetradecyl aminobutyroylvalylamino butyric ureatrifluoroacetate to promote hyaluronic acid production in skin; and (c)an effective amount of tripeptide-1 to promote hyaluronic acidproduction in skin.
 2. The method of claim 1, wherein the composition isapplied to a deep line or wrinkle, and wherein the composition reducethe appearance of said deep line or wrinkle.
 3. The method of claim 2,wherein the tripeptide-1 promotes collagen I, collagen III, laminin, andfibronectin production in the skin.
 4. The method of claim 3, whereinthe composition includes 0.01 to 1% by weight of Centella asiatica stemcells, 0.0001 to 1% by weight of tetradecyl aminobutyroylvalylaminobutyric urea trifluoroacetate, and 0.00001 to 1% by weight oftripeptide-1.
 5. The method of claim 4, wherein the composition isapplied to facial skin or neck skin.
 6. The method of claim 5, whereinthe composition is a cream or lotion or a water-in-oil emulsion.
 7. Themethod of claim 6, wherein after topical application the compositionremains on the skin for at least 30 minutes.
 8. The method of claim 7,wherein the composition further comprises: (d) encapsulated retinol; (e)Punica granatum extract or sterols thereof; Codium tomentosum extract;(g) Cinnamomum Cassia bark extract; and (h) Glycyrrhiza glabra rootextract.
 9. The method of claim 1, wherein: the Centella asiatica stemcells is a mixture of Centella asiatica stem cells, glycerin, andxanthan gum; the tetradecyl aminobutyroylvalylamino butyric ureatrifluoroacetate is a mixture of tetradecyl aminobutyroylvalylaminobutyric urea trifluoroacetate, magnesium chloride, glycerin, and water;and the tripeptide-1 is a mixture of tripeptide-1, water, urea, glucose,and guanidine HCL.
 10. The method of claim 1, wherein the composition isa cleanser that comprises 0.0001 to 1% by weight of Centella asiaticastem cells, 0.00001 to 1% by weight of tetradecylaminobutyroylvalylamino butyric urea trifluoroacetate, and 0.000001 to1% by weight of tripeptide-1.
 11. The method of claim 10, furthercomprising glycerin and water.